bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B020: A clinically relevant orthotopic endometrial carcinosarcoma mouse model using human patient-derived organoids
Authors: Gorman Megan , Gowthaman Divya , Katcher Arielle , Chung Charlie , Yueh Brian , Barbi Mali , Garcia Libia , Frimer Marina , Goldberg Gary L. , Beyaz Semir
Published: March 2024

Uterine carcinosarcoma (CS) is a rare but aggressive endometrial malignancy. The incidence of CS has been increasing and is projected to continue to rise. African American women in particular have an increased incidence of CS and overall increased mortality related to endometrial cancer, underscoring known disparities in cancer care across racial and ethnic groups. Compared to other histologic subtypes, CS remains rare and understudied on a molecular and cellular basis, and under-represented in clinical trials. Therefore, current treatment therapies available for CS have been extrapolated from treatments used in other histologies of endometrial cancer, highlighting a significant need for effective treatment targeted at this subtype. Due to this paucity of data surrounding targeted therapies for CS, patients who are diagnosed with this aggressive and lethal cancer tend to have worse outcomes. We have developed a clinically relevant CS murine model by injecting human CS patient-derived organoids (PDO) from diverse ancestries into the endometrium of immunocompromised mice. Tumor progression in the mice was monitored with physical examination, PET/CT scan, contrast enhanced CT scan, ultrasound, and bioluciferase imaging. The tumor was established after three months, and the mice were sacrificed following the experiment. The diagnosis of invasive CS was confirmed by macroscopic and histologic analyses in the orthotopic model. Our orthotopic CS PDO transplantation model has many potential applications for studying tumor biology of CS in the pre-clinical setting. Future directions include trialing the efficacy of standard of care chemotherapy in the orthotopic model. Using this model, we aim to identify targeted therapy for CS and potentially advance to Phase I human clinical trials.

Citation Format: Megan Gorman, Divya Gowthaman, Arielle Katcher, Charlie Chung, Brian Yueh, Mali Barbi, Libia Garcia, Marina Frimer, Gary L. Goldberg, Semir Beyaz. A clinically relevant orthotopic endometrial carcinosarcoma mouse model using human patient-derived organoids [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 B020.
Abstract IA003: The future of endometrial cancer research: possibility and purpose
Authors: Doll Kemi
Published: March 2024

This talk will review the growing problem of endometrial cancer in the United States, discussing the state of the science, ongoing investigations, and promises of future progress along the entire endometrial cancer care continuum. An emphasis on health equity, workforce diversity, and patient-centeredness will be included.

Citation Format: Kemi Doll. The future of endometrial cancer research: possibility and purpose [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 IA003.
Abstract IA011: Understanding field carcinogenesis in obesity-related endometrial cancer
Authors: Chandler Ronald
Published: March 2024

Over the last decade, endometrial cancer (EC) incidence has increased at an average rate of 0.8% each year. Although cancer death rates decreased during this time, EC showed the greatest increase in cancer death among women. Public awareness of EC remains low, and EC research remains underfunded relative to its societal burden. While most women with EC are post-menopausal, up to 30% of cases occur in pre-menopausal women under 50 years of age, with obesity being a major risk factor. More than half of all EC is associated with obesity. Obesity is also a leading risk factor for benign endometrial hyperplasia, which is considered the precursor lesion to EC. Like other cancers, the causes of EC are multifactorial, with obesity and somatic mutations playing causal roles. By 2030, half of all adult women in the U.S. are expected to be classified as obese. Therefore, EC incidence is expected to increase. If detected early, EC can be cured with surgical hysterectomy, but this solution is not ideal for all women. Intentional weight loss can lower endometrial cancer risk in obese women, but certain barriers prevent obese, at-risk women from losing weight or maintaining healthy lifestyles while living in obesogenic environments. There is a critical need to understand the biological mechanisms underlying EC pathogenesis in at-risk obese women. Although EC is thought to arise from a hyperplastic endometrial epithelium, our previous findings suggest that high-fat diet induced obesity affects other cell types within the endometrial microenvironment, including endometrial stroma and immune cells, in the absence of histopathological change. Common EC somatic mutations can also arise in the absence of histopathological change or occur in cases of benign disease. Our overarching hypothesis is that a normal appearing endometrium may accrue cell-context dependent alterations in response to obesity and somatic mutations across a pre-malignant tissue field that are predictive of malignant transformation. This presentation will highlight our recent work on the combined molecular and phenotypic effects of obesity and common EC driver mutations on the endometrial tissue field. The identification of high-value molecular targets across the endometrial pre-malignant field may inform new early detection and prevention strategies for EC.

Citation Format: Ronald Chandler. Understanding field carcinogenesis in obesity-related 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 IA011.
Abstract IA013: Unique metabolic changes in Lynch syndrome-associated endometrial cancer
Authors: Yates Melinda S.
Published: March 2024

Lynch syndrome-associated endometrial cancers (ECs) are defined by germline mutations in DNA mismatch repair genes, including MSH2, MSH6, PMS2, and MLH1. Lynch syndrome (LS) tumors have received increased attention in the therapeutic context as these tumors are microsatellite instable and often reflect increased immune cell infiltration and enhanced response to immunotherapy. However, relatively little attention has been paid to pathogenesis of LS ECs. Women with LS represent an at-risk population who could benefit from cancer interception strategies due to a 60% cumulative lifetime risk of developing EC. We developed a mouse model of MSH2 loss targeted to the uterus to evaluate EC pathogenesis, with the goal of elucidating mechanisms that alter disease penetrance for women with hereditary risk for EC development. Our Progesterone Receptor-Cre Msh2f lox/flox mice (abbreviated Msh2KO) develop ECs that closely mimic human EC. Whole transcriptome profiling of Msh2KO EC and Msh2KO normal endometrium compared to wild-type endometrium identified “Mitochondrial dysfunction” as a significantly altered pathway in Msh2 deficiency, prompting our in-depth evaluation of mitochondrial alterations in Msh2KO mice, MSH2-deficient cell lines, and LS-associated EC patient specimens. We will discuss the impact of MSH2 deficiency across multiple measures of mitochondrial content, integrity, function, and metabolomic analyses in ECs using preclinical models and human tissue studies. Overall, our studies reveal that MSH2-deficient EC is characterized by mitochondrial DNA damage, mitochondrial content reduction, and decreased mitochondrial function. In addition, decreased mitochondrial respiration for energy production facilitates metabolic reprogramming toward glycolysis. We are conducting further studies to define mechanisms underlying mitochondrial defects due to MSH2 loss and opportunities for intervention. Mitochondrial and metabolic aberrations could serve as novel biomarkers for EC development and targets for cancer prevention in women with LS.

Citation Format: Melinda S. Yates. Unique metabolic changes in Lynch syndrome-associated 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 IA013.
Abstract IA016: Molecular diversity of uterine serous carcinoma
Authors: Santin Alessandro D.
Published: March 2024

Uterine serous carcinoma (USC) is a biologically aggressive subtype of endometrial cancer with a high recurrence rate and poor prognosis disproportionately affecting black women. Whole-exome-sequencing analysis revealed that up to 10% of USC harbor features of ultra/hypermutation due to a deficiency of polymerase e (POLE) and/or mismatched-repair genes (MMRd). These tumors are notable for having a high number of single nucleotide variants (SNV), no LOH segments or copy-number variants (CNV) and a peculiar genetic signature characterized by an increased rate of C > A transversions. In contrast, the overwhelming majority of USC (~ 90%) are POLE/MMR proficient, have a low number of SNV and demonstrate alteration in genes including TP53, PIK3CA mutation/amplification, ERBB2 amplification, CCNE1 amplification, FBXW7 mutation/deletion, PPP2R1A mutation, and somatic mutations involving homologous recombination genes. Frequent mutations in CHD4/Mi2b, a member of the NuRD-chromatin-remodeling-complex, and TAF1, an element of the core TFIID transcriptional machinery are also detected in a significant number of USC. Somatic CNVs, a sign of genomic instability, are identified in the majority of USC with multiple copy number gains and copy number losses, with the most frequent events taking place in pathways similar to those found from analysis of SNVs. In addition to loss of TP53, frequent deletion of a small segment of chromosome 19 containing MBD3, a member of the NuRD-chromatin-modification-complex, and frequent amplification of chromosome segments containing PIK3CA, ERBB2 (encoding for the HER2/neu receptor) and CCNE1 (a target of FBXW7-mediated ubiquitination) are commonly detected. Overall, these findings suggest that both somatic point mutations (SNV) and somatic CNV play a major role in the pathogenesis of USC. Importantly, the frequent mutation of DNA damage, chromatin remodeling, cell cycle and cell proliferation pathways in USC including the overexpression/amplification of HER2/neu, CCNE1 and the tumor-associated calcium signal transducer 2 (TACSTD2/TROP2) genes, suggest novel targets for therapy against this lethal variant of endometrial cancer.

Citation Format: Alessandro D. Santin. Molecular diversity of uterine serous 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 IA016.
Supplementary Figures S1-S7 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

Supp. Fig. 1 Differential methylation across prostate cancer disease states
Supp. Fig. 2 NEMO panel design
Supp. Fig. 3 Tumor content estimation with a minimal set of informative regions
Supp. Fig. 4 Scoring CRPC-NE in circulation with the phenotype evidence (PE) score
Supp. Fig. 5 Probing the CRPC spectrum with NEMO
Supp. Fig. 6 Clinical utility of the NEMO assay
Supp. Fig. 7 Copy number estimation using the NEMO assay
Figure 3 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

TIS after INX-315 treatment of CCNE1-amplified cancers. A, Left, representative images after staining OVCAR3 and MKN1 cells for beta-galactosidase activity after treatment with INX-315 (scale bar = 100 μm). Experiments performed with three technical replicates. Right, quantification of integrated beta-galactosidase signal per cell. Dashed line indicates cutoff used to define beta-galactosidase positivity, and numbers represent percentage of beta-galactosidase–positive cells. B, Left, representative images after staining OVCAR3 and MKN1 cells with DAPI and phalloidin after treatment with INX-315 (scale bar = 100 μm). Right, quantification of relative nuclear size based on DAPI staining. Experiments performed with three technical replicates. C, ssGSEA scores derived from RNA sequencing of OVCAR3 cells treatment with control or INX-315 300 nmol/L for seven days. Scores are calculated for four independent senescence-associated gene sets; three technical replicates. D, GSEA plots derived from RNA-sequencing performed on tumor tissue from experiments in Fig. 2D and E. Normalized enrichment score (NES) and q value (false discovery rate) were calculated as described in Methods (all P values were calculated using unpaired t tests, error bars represent SD). E, ssGSEA scores for four senescence-associated gene signatures were calculated from RNA-sequencing on OV5398 PDX tumor tissue. Heat map shows z-scores for these. Bar plot above shows mean z-score for each sample across all signatures. F, GSEA plots derived from RNA-sequencing performed on tumor tissue from experiments in Fig. 2D and E. NES and q value (false discovery rate) were calculated as described in Methods (all P values were calculated using unpaired t tests, error bars represent SD).
Supplementary Table S6 from Targeting DHX9 Triggers Tumor-Intrinsic Interferon Response and Replication Stress in Small Cell Lung Cancer
Authors: Murayama Takahiko , Nakayama Jun , Jiang Xinpei , Miyata Kenichi , Morris Alexander D. , Cai Kathy Q. , Prasad Rahul M. , Ma Xueying , Efimov Andrey , Belani Neel , Gerstein Emily R. , Tan Yinfei , Zhou Yan , Kim William , Maruyama Reo , Campbell Kerry S. , Chen Lu , Yang Yibin , Balachandran Siddharth , Cañadas Israel
Published: March 2024

Flow cytometry settings
Supplementary Table S5 from Targeting DHX9 Triggers Tumor-Intrinsic Interferon Response and Replication Stress in Small Cell Lung Cancer
Authors: Murayama Takahiko , Nakayama Jun , Jiang Xinpei , Miyata Kenichi , Morris Alexander D. , Cai Kathy Q. , Prasad Rahul M. , Ma Xueying , Efimov Andrey , Belani Neel , Gerstein Emily R. , Tan Yinfei , Zhou Yan , Kim William , Maruyama Reo , Campbell Kerry S. , Chen Lu , Yang Yibin , Balachandran Siddharth , Cañadas Israel
Published: March 2024

CRISPR screen results
Supplementary Table S2 from Targeting DHX9 Triggers Tumor-Intrinsic Interferon Response and Replication Stress in Small Cell Lung Cancer
Authors: Murayama Takahiko , Nakayama Jun , Jiang Xinpei , Miyata Kenichi , Morris Alexander D. , Cai Kathy Q. , Prasad Rahul M. , Ma Xueying , Efimov Andrey , Belani Neel , Gerstein Emily R. , Tan Yinfei , Zhou Yan , Kim William , Maruyama Reo , Campbell Kerry S. , Chen Lu , Yang Yibin , Balachandran Siddharth , Cañadas Israel
Published: March 2024

PCR primer sequences
Supplementary Table S4 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 S4 Assembly enrichment in replication and drug sensitivity screens.xlsx
Supplementary Figure S7 from Targeting DHX9 Triggers Tumor-Intrinsic Interferon Response and Replication Stress in Small Cell Lung Cancer
Authors: Murayama Takahiko , Nakayama Jun , Jiang Xinpei , Miyata Kenichi , Morris Alexander D. , Cai Kathy Q. , Prasad Rahul M. , Ma Xueying , Efimov Andrey , Belani Neel , Gerstein Emily R. , Tan Yinfei , Zhou Yan , Kim William , Maruyama Reo , Campbell Kerry S. , Chen Lu , Yang Yibin , Balachandran Siddharth , Cañadas Israel
Published: March 2024

DHX9-low tumors are associated with interferon and inflammatory signatures
Supplementary Figure S6 from Targeting DHX9 Triggers Tumor-Intrinsic Interferon Response and Replication Stress in Small Cell Lung Cancer
Authors: Murayama Takahiko , Nakayama Jun , Jiang Xinpei , Miyata Kenichi , Morris Alexander D. , Cai Kathy Q. , Prasad Rahul M. , Ma Xueying , Efimov Andrey , Belani Neel , Gerstein Emily R. , Tan Yinfei , Zhou Yan , Kim William , Maruyama Reo , Campbell Kerry S. , Chen Lu , Yang Yibin , Balachandran Siddharth , Cañadas Israel
Published: March 2024

DHX9 loss decreases tumor growth, induces immune cell infiltration and enhances response to immunotherapy
Supplementary Figures S1-6 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

Supplementary Figure S1. Aspects of replication stress addressed by cancer therapeutics.
Supplementary Figure S2. Nested systems in tumors (NeST).
Supplementary Figure S3. VNN schematic.
Supplementary Figure S4. Performance and interpretation of the multi-drug VNN.
Supplementary Figure S5. Evaluation of assemblies by systematic drug sensitivity screens.
Supplementary Figure S6. Survival analysis of cisplatin-treated TCGA cohorts.
Supplementary Figure S2 from Targeting DHX9 Triggers Tumor-Intrinsic Interferon Response and Replication Stress in Small Cell Lung Cancer
Authors: Murayama Takahiko , Nakayama Jun , Jiang Xinpei , Miyata Kenichi , Morris Alexander D. , Cai Kathy Q. , Prasad Rahul M. , Ma Xueying , Efimov Andrey , Belani Neel , Gerstein Emily R. , Tan Yinfei , Zhou Yan , Kim William , Maruyama Reo , Campbell Kerry S. , Chen Lu , Yang Yibin , Balachandran Siddharth , Cañadas Israel
Published: March 2024

Induction of IFN response after DHX9 loss in SCLC cell lines
Supplementary Figure S1 from Targeting DHX9 Triggers Tumor-Intrinsic Interferon Response and Replication Stress in Small Cell Lung Cancer
Authors: Murayama Takahiko , Nakayama Jun , Jiang Xinpei , Miyata Kenichi , Morris Alexander D. , Cai Kathy Q. , Prasad Rahul M. , Ma Xueying , Efimov Andrey , Belani Neel , Gerstein Emily R. , Tan Yinfei , Zhou Yan , Kim William , Maruyama Reo , Campbell Kerry S. , Chen Lu , Yang Yibin , Balachandran Siddharth , Cañadas Israel
Published: March 2024

DHX9 suppresses ERE-derived dsRNA accumulation in SCLCs
Figure S9 from EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth
Authors: Kuhlmann-Hogan Alexandra , Cordes Thekla , Xu Ziyan , Kuna Ramya S. , Traina Kacie A. , Robles-Oteíza Camila , Ayeni Deborah , Kwong Elizabeth M. , Levy Stellar , Globig Anna-Maria , Nobari Matthew M. , Cheng George Z. , Leibel Sandra L. , Homer Robert J. , Shaw Reuben J. , Metallo Christian M. , Politi Katerina , Kaech Susan M.
Published: March 2024

Figure S9: Statins inhibit EGFRmutant tumor cell growth and oncogenic signaling.
Figure S4 from EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth
Authors: Kuhlmann-Hogan Alexandra , Cordes Thekla , Xu Ziyan , Kuna Ramya S. , Traina Kacie A. , Robles-Oteíza Camila , Ayeni Deborah , Kwong Elizabeth M. , Levy Stellar , Globig Anna-Maria , Nobari Matthew M. , Cheng George Z. , Leibel Sandra L. , Homer Robert J. , Shaw Reuben J. , Metallo Christian M. , Politi Katerina , Kaech Susan M.
Published: March 2024

Figure S4: Deficiency of PPARγ in CSF1R- or CD11c-expressing cells suppresses tumor growth. 
Figure S2 from EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth
Authors: Kuhlmann-Hogan Alexandra , Cordes Thekla , Xu Ziyan , Kuna Ramya S. , Traina Kacie A. , Robles-Oteíza Camila , Ayeni Deborah , Kwong Elizabeth M. , Levy Stellar , Globig Anna-Maria , Nobari Matthew M. , Cheng George Z. , Leibel Sandra L. , Homer Robert J. , Shaw Reuben J. , Metallo Christian M. , Politi Katerina , Kaech Susan M.
Published: March 2024

Figure S2: Innate immune cells are regulated by GM-CSF and contributes to tumorigenesis.
Figure 1 from Passenger Gene Coamplifications Create Collateral Therapeutic Vulnerabilities in Cancer
Authors: Bei Yi , Bramé Luca , Kirchner Marieluise , Fritsche-Guenther Raphaela , Kunz Severine , Bhattacharya Animesh , Rusu Mara-Camelia , Gürgen Dennis , Dubios Frank P.B. , Köppke Julia K.C. , Proba Jutta , Wittstruck Nadine , Sidorova Olga Alexandra , Chamorro González Rocío , Dorado Garcia Heathcliff , Brückner Lotte , Xu Robin , Giurgiu Mădălina , Rodriguez-Fos Elias , Yu Qinghao , Spanjaard Bastiaan , Koche Richard P. , Schmitt Clemens A. , Schulte Johannes H. , Eggert Angelika , Haase Kerstin , Kirwan Jennifer , Hagemann Anja I.H. , Mertins Philipp , Dörr Jan R. , Henssen Anton G.
Published: March 2024

Overview of the systematic approach to identify collateral lethal dependencies associated with passenger gene coamplifications in cancers.
Supplementary Table 6 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

ssGEA signatures derived from snRNA-seq data.
Table S5 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 S5 shows baseline patient and tumor characteristics in high risk patients
Figure 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

Figure S3 shows that prophylactic steroids do not improve efficacy outcomes in high risk patients
Figure S1 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

Figure S1 shows the serum markers associated with severe CRS and ICANS
Supplementary Tables 1 and 2 from IDH1-Mutant Preleukemic Hematopoietic Stem Cells Can Be Eliminated by Inhibition of Oxidative Phosphorylation
Authors: Landberg Niklas , Köhnke Thomas , Feng Yang , Nakauchi Yusuke , Fan Amy C. , Linde Miles H. , Karigane Daiki , Lim Kelly , Sinha Rahul , Malcovati Luca , Thomas Daniel , Majeti Ravindra
Published: March 2024

Supplementary Table 1.
Clinical characteristics of the 17 IDH-mutant AML patients assessed.
Supplementary Table 2.
Summary of antibodies and flow cytometry reagents.
Supplementary Figures 1-6 from IDH1-Mutant Preleukemic Hematopoietic Stem Cells Can Be Eliminated by Inhibition of Oxidative Phosphorylation
Authors: Landberg Niklas , Köhnke Thomas , Feng Yang , Nakauchi Yusuke , Fan Amy C. , Linde Miles H. , Karigane Daiki , Lim Kelly , Sinha Rahul , Malcovati Luca , Thomas Daniel , Majeti Ravindra
Published: March 2024

Supplementary Figure 1. IDH2 is mutated in preleukemic hematopoietic stem cells in relapse causing clones in AML.
Supplementary Figure 2. Single-cell RNA sequencing and combined genotyping reveal distinct transcriptomic profiles of IDH1-mutant pHSCs in AML
Supplementary Figure 3. Modeling human pHSCs using CRISPR/Cas9 with HDR show reduced proliferation and blocked differentiation caused by IDH1 mutations
Supplementary Figure 4. IDH1 mutations reduce 5-hydroxymethylcytosine in gene bodies
Supplementary Figure 5. IDH1 mutations drives transcriptomic alterations
Supplementary Figure 6. IDH1-mutant pHSCs are sensitive to inhibition of oxidative phosphorylation
Data from Synergistic Drug Combinations Promote the Development of Resistance in Acute Myeloid Leukemia
Authors: Mason-Osann Emily , Pomeroy Amy E. , Palmer Adam C. , Mettetal Jerome T.
Published: March 2024

Abstract
Combination therapy is an important part of cancer treatment and is often employed to overcome or prevent drug resistance. Preclinical screening strategies often prioritize synergistic drug combinations; however, studies of antibiotic combinations show that synergistic drug interactions can accelerate the emergence of resistance because resistance to one drug depletes the effect of both. In this study, we aimed to determine whether synergy drives the development of resistance in cancer cell lines using live-cell imaging. Consistent with prior models of tumor evolution, we found that when controlling for activity, drug synergy is associated with increased probability of developing drug resistance. We demonstrate that these observations are an expected consequence of synergy: the fitness benefit of resisting a drug in a combination is greater in synergistic combinations than in nonsynergistic combinations. These data have important implications for preclinical strategies aiming to develop novel combinations of cancer therapies with robust and durable efficacy.
Significance:
Preclinical strategies to identify combinations for cancer treatment often focus on identifying synergistic combinations. This study shows that in AML cells combinations that rely on synergy can increase the likelihood of developing resistance, suggesting that combination screening strategies may benefit from a more holistic approach rather than focusing on drug synergy.

See related commentary by Bhola and Letai, p. 81.

This article is featured in Selected Articles from This Issue, p. 80
Supplementary Methods 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

Supplementary Methods
FIGURE 8 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

Potential model-based biomarkers of higher-risk prostate cancer. A–F, Distribution of six potential model-based biomarkers in lower-risk (n = 8) and higher-risk (n = 8) prostate cancer, which were defined as tumors with GS = 3 + 3 and GS ≥ 3 + 4, respectively. These model-based biomarkers were calculated at the times were both a histopathologic assessment and imaging measurement are available for each patient in the cohort (n = 7). In particular, the model-based markers in A–F are: prostate volume (VP), tumor volume, total tumor cell volume (VN), mean normalized tumor cell density (), total tumor index (NT), and mean proliferation activity of the tumor (Ap). Outliers are represented as hollow circles and an asterisk indicates significance under a one-sided Wilcoxon rank-sum test (P < 0.05). G, ROC curves for (i) the univariate logistic regression model constructed using the mean proliferation activity of the tumor (i.e., the only model-based marker that was significantly different between lower-risk prostate cancer and higher-risk prostate cancer), and (ii) the bivariate logistic regression model constructed using the mean proliferation activity of the tumor and the total tumor index (which is the combination of model-based markers that rendered the highest performance). The AUC of each ROC curve is reported within the plot, and the optimal performance point for both the univariate and bivariate logistic regression models operates at 75% sensitivity and specificity (bullet points on the ROC curves).
FIGURE 4 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

Examples of personalized calculations of prostate cancer growth in the global calibration scenario. A–D, Prostate cancer growth at the dates of the second mpMRI scan during model calibration (tMRI,2; upper row in each panel) and the third mpMRI scan (tMRI,3; bottom row in each panel) in 4 patients. These results are illustrated using a 3D representation of the mpMRI-extracted prostate geometry of each patient including the imaging-measured and model-calculated tumor regions (red and blue volumes), along with an axial section of the prostate showing the normalized tumor cell density map obtained from the mpMRI data and using the personalized model (i.e., Eq. (3)).
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

Active surveillance (AS) is a suitable management option for newly diagnosed prostate cancer, which usually presents low to intermediate clinical risk. Patients enrolled in AS have their tumor monitored via longitudinal multiparametric MRI (mpMRI), PSA tests, and biopsies. Hence, treatment is prescribed when these tests identify progression to higher-risk prostate cancer. However, current AS protocols rely on detecting tumor progression through direct observation according to population-based monitoring strategies. This approach limits the design of patient-specific AS plans and may delay the detection of tumor progression. Here, we present a pilot study to address these issues by leveraging personalized computational predictions of prostate cancer growth. Our forecasts are obtained with a spatiotemporal biomechanistic model informed by patient-specific longitudinal mpMRI data (T2-weighted MRI and apparent diffusion coefficient maps from diffusion-weighted MRI). Our results show that our technology can represent and forecast the global tumor burden for individual patients, achieving concordance correlation coefficients from 0.93 to 0.99 across our cohort (n = 7). In addition, we identify a model-based biomarker of higher-risk prostate cancer: the mean proliferation activity of the tumor (P = 0.041). Using logistic regression, we construct a prostate cancer risk classifier based on this biomarker that achieves an area under the ROC curve of 0.83. We further show that coupling our tumor forecasts with this prostate cancer risk classifier enables the early identification of prostate cancer progression to higher-risk disease by more than 1 year. Thus, we posit that our predictive technology constitutes a promising clinical decision-making tool to design personalized AS plans for patients with prostate cancer.

Significance:

Personalization of a biomechanistic model of prostate cancer with mpMRI data enables the prediction of tumor progression, thereby showing promise to guide clinical decision-making during AS for each individual patient.
Ativismo imigrante e estratégias emocionais para a deliberação on-line: o caso da página Brasileiras não se calam
Authors: Zanetti Lucas Arantes
Published: March 2024

This paper investigates how mediatization theories, and the notion of public sphere and deliberation are articulated by personal narratives as an emotional discursive strategy and interactional device aimed at online deliberation. For this purpose, we examine the case of the Instagram page “Brasileiras não se calam,” an activist organization that denounces cases of misogyny and xenophobia experienced by Brazilian women in Europe. Specifically, we analyze the commentaries under a harassment report. As a result, we argue that the personal report is an important interactional device for fostering public debate and for developing concrete activist actions against discriminatory situations.
Saúde mental no Twitter: análise de manifestações por meio de mineração de dados
Authors: Correia Geovana Pereira , Mendonça Rhayssa Fernandes , Borges Rosana Maria Ribeiro , Cordeiro Douglas Farias
Published: March 2024

Este artículo se centra en las manifestaciones relacionadas con la salud mental en la red social Twitter. Su objetivo es analisar las publicaciones que utilizan el hashtag #saudemental, en el período de enero de 2020 a junio de 2022. Para ello, se realizó una investigación bibliográfica que permitió fundamentar teóricamente las ideas presentadas en un análisis de los contenidos que circularon por uso del hashtag. El procesamiento de contenidos se realizó mediante el instrumento metodológico conocido como Descubrimiento de Conocimiento en Bases de Datos (KDD), el cual es una solución para generar información y exploración analítica basada en la minería de datos. Los análisis revelan el predominio de contenidos vinculados a las campañas Septiembre Amarillo y Enero Blanco, la expresión individual de sentimientos, la asociación con la superación y la identificación de tabúes y estereotipos.
Notas sobre expropriação, alteridade e legibilidade: fotografias de conflito, imperialismo e destruição
Authors: Lins Marcela Barbosa , Duarte Mariana Falcão , Oliveira Marianna Rungue de , Marques Ângela Cristina Salgueiro
Published: March 2024

Este artigo busca tecer reflexões sobre expropriação, alteridade e legibilidade na fotografia de guerra contemporânea, a partir da análise de três imagens premiadas pelo prêmio Pulitzer 2023. Esse exercício é realizado por meio de um diálogo crítico com autoras como Ariella Azoulay, Marie-José Mondzain e Susan Sontag. Defendemos que, a despeito de uma potência da imagem de gerar conflito e produzir outras visibilidades, as imagens aqui apresentadas revelam pouca margem para rearticular relações de poder, alterar imaginários e desestabilizar formas consensuais de pensar a experiência.
Crimes, risos e tensão: considerações acerca do humor em podcasts brasileiros de true crime
Authors: Jáuregui Carlos
Published: March 2024

This work reflects on humorous elements present in audio accounts of real crimes. With this objective, we identified a set of rhetorical and expressive procedures related to humor in the podcasts Modus Operandi and Café com Crime, which characterize these accounts both in verbal and in specifically sound aspects. Based on this, we present contributions to the theory of true crime, which describes typical narrative codes of the genre, and we observe an effort by these podcasts to balance narrative tension and comedy. We also see the possibility of subverting the concept of comic relief to give way to strategies of dramatic safeguarding with the function of setting limits to laughter withinthis genre. Finally, we raise possible paths for the ethical debates.
Redescription of Xiphinema artemisiae Chizhov, Tiev & Turkina, 1986 (Dorylaimida: Longidoridae): new occurrence in Iran
Authors: Fekrat Farnaz , Ghaderi Reza , Pourjam Ebrahim , Castillo Pablo , Pedram Majid
Published: March 2024

A population of Xiphinema artemisiae was recovered from Iran, representing the first report after its original description from a meadow pasture in northern Caucasus, Russia. The Iranian population was recovered from the rhizosphere of grasses in the Damavand region, Tehran province. The females of the recovered populations are characterised by a lip region separated from the rest of body by a depression, a 5.1-5.6 mm long body, a 129-138 μm long odontostyle, 76-85 μm long odontophore, a uterus having a pseudo-Z-organ and crystalloid bodies observed in some specimens, and a short, rounded, dorsally more convex tail with a subcentral mucron, four juvenile developmental stages (the first stage was not recovered) and functional males. The Iranian population is morphologically and morphometrically similar to the type population and minor morphological differences can be attributed to geographical interpopulation differences. Molecular phylogenetic relationships of the Iranian population of X. artemisiae with other species were reconstructed using sequences of three genomic ribosomal markers, viz. small, large subunit D2-D3 and internal transcribed spacer (SSU, LSU D2-D3 and ITS) rDNA.
Hip abductor strengthening vs iliotibial band stretching exercises in conventional knee osteoarthritis rehabilitation: a comparative trial
Authors: Mehla P. , Joshi S. , Pawalia A. , Gera C.
Published: March 2024

The aim of this study is to compare the effect of hip abductor and iliotibial band (ITB) exercises for patients of knee osteoarthritis (OA). 60 patients with knee OA were randomly divided into three groups. Group A received hip abductor strengthening along with quadriceps strengthening exercises, Group B received iliotibial band stretching along with quadriceps strengthening exercises and Group C received conventional knee exercises. The treatment duration was three sessions per week in alternate days for 3 weeks. The outcome measures were pain, physical performance and quality of life, which were evaluated at the baseline and after 3 week of intervention with the visual analogue scale, chair sit to stand test and knee injuries and osteoarthritis outcome score questionnaire. All the three groups showed statistically significant improvement in pain, physical performance and quality of life in patients with knee OA. Hip abductor strengthening exercises group showed more significant improvement in pain, physical performance and quality of life than the Iliotibial band stretching exercises group. The results of the study suggest that the hip abductor strengthening exercises can be more effective than iliotibial band stretching exercises in reducing pain, improving quality of life and physical performance in patients with knee osteoarthritis. But we can also use iliotibial band stretching exercises with other interventions in case of knee OA because iliotibial band stretching exercises also gives result in reduction of pain, symptoms and improvement in physical performance and quality of life.

Clinical trial registry of India No. CTRI/2023/06/054225
Continuity and Change in the Role of Mysticism Under the Islamic Republic of Iran
Authors: Machlis Elisheva
Published: March 2024

The current study will evaluate the role of ‘irfān [the inner perception of knowledge; combining elements of philosophy, theosophy, mysticism and Shi‘i thought] within the Islamic Republic of Iran as a significant component of Iran’s cultural heritage. It will focus on several prominent clerics and intellectuals who represent the regime’s diverse political factions. This article will demonstrate that under the Islamic Republic, ‘irfān evolved from a marginalized area to a central phenomenon and became a tool to debate the political direction of the state and the relationship between its revolutionary and republican elements. While mysticism in the service of politics was more wide-spread among the reformist camp, ardent supporters of the regime resorted to ‘irfān to enhance an exclusive perception of authority based on the rule of the Supreme Jurist. It also created a shared spiritual basis among the Islamic State’s diverse voices. The result was a new blend between mysticism, philosophy, Western thought, politics, Islamic law, and even messianism, within an inter-connectivity between the mystical path and the Shari‘a. Consequently, a complex understanding of ‘irfān has to take into consideration the multiple fusions between Islamic mysticism and other trends and evaluate the result in a specific socio-political context.
Expecting the Future: Entropy-Based Predictions in Time Perception
Authors: Clarke Jason , Tyler Becky
Published: March 2024

What cognitive mechanisms underlie the human experience of time’s directionality, often described as the psychological arrow of time? This study explores this question by examining the role of visual entropy, a measure of disorder within a system, in shaping our perception of time. Grounded in the second law of thermodynamics and predictive processing frameworks, we hypothesised that the human cognitive system expects an increase in visual entropy over time and that violations of this expectation (prediction errors) would lead to a relative overestimation of perceived duration. Participants reproduced the duration of computer-generated animations depicting three-dimensional greyscale shapes shattering from wholes into parts (low to high entropy) or the reverse (high to low entropy) presented at different lengths (500, 1000, 1500, and 2000 milliseconds). The results revealed a significant interaction: while forward animations (low to high entropy) were perceived as longer at the shortest duration (500 ms), backward animations (high to low entropy) were overestimated at longer durations (1500 and 2000 ms). This pattern suggests an initial reliance on high-precision expectations for shorter stimuli, with a shift towards increased weighting of prediction errors for longer durations, leading to the overestimation of entropy-reversed stimuli. These results align with predictive processing frameworks, indicating that the brain dynamically reconciles incoming sensory data with prior expectations of entropy progression, thereby shaping our subjective experience of temporal directionality. This research introduces a novel paradigm for examining time perception and supports the application of predictive processing theories in understanding the cognitive and neural underpinnings of temporal experience.
Understanding the Geopolitical Implications of the Impending Religious Power Vacuum in Tibet
Authors: Ba Jonathan
Published: March 2024

Despite being the smallest branch of Buddhism worldwide, Vajrayana Buddhism is the majority religion in Tibet, Mongolia, and Bhutan, where it wields significant religious and political power. This power has traditionally been concentrated among a small number of lamas, most notably the Dalai Lama, who upon their passing are replaced by a successor in accordance with traditional rituals. Since Tibet came under control of China in 1950, the Chinese Communist Party has sought to gain complete control over Tibetan Vajrayana Buddhism, coopting these leadership institutions by installing its own puppet lamas. However, the flight of the current Dalai Lama from the Tibetan capital Lhasa in 1959 led to the exodus of Tibetans to India, where a government-in- exile was established in Dharamsala. This government, which derives its legitimacy from the Dalai Lama, represents the interests of the Tibetan people, including challenging Chinese rule over Tibet. The current Dalai Lama is now an octogenarian, and his passing will create a religious power vacuum at the core of Vajrayana Buddhism. This paper explores several possible outcomes of this religious power vacuum, and whether Vajrayana Buddhism can maintain its integrity and autonomy moving forward.
The change of physical properties of calcium carbonate nanomaterials cured soil in road substrates
Authors: Guo Guoying , Li Xin , Guo Wenjun , Yang Ling , Wang Wei
Published: March 2024

The utilization of appropriate materials to enhance road subgrade’s physical characteristics is crucial for current transportation construction and maintenance. This study proposes a curing method that employs calcium carbonate nanomaterials to address the problem of soil displacement
and settlement in roadway subgrades. A method was developed during the study to explore the optimal curing material ratio. Additionally, this study developed a method for testing and analyzing the mechanical properties of soils cured with nanomaterials, including measures of tensile stress,
triaxial shear stress, and Moore’s damage envelope. The study demonstrated that the unconfined compressive strength of the soil treated with calcium carbonate nanomaterials was 0.40 MPa after 7 days of curing with a 6% doping of the curing agent. Increasing the doping to 18% resulted
in a breaking load of the soil reaching 0.100 kN. Furthermore, the triaxial shear stress–strain curve of the soil exhibited a slope of 264.47 during the linear phase when the curing agent was dosed at 6%. The slope of the linear phase of the stress–strain curve for triaxial shear
at 6% curing agent doping was found to be 264.47. The cured soil molar pack line exhibited an internal friction angle of 22.66 degrees at the same curing agent dosage. The displacement analysis of the replacement roadbed with cured soil revealed a maximum observed displacement of only 377
mm after filling the embankment using the study method. The experimental results provide support for the hypothesis of the study, which suggests that the application of calcium carbonate nanoparticles can significantly enhance the physical characteristics of road subgrade.