bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from SPOP mutations target STING1 signaling in prostate cancer and create therapeutic vulnerabilities to PARP inhibitor–induced growth suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilie Patrick G. , Thompson Timothy C.
Published: November 2023

Abstract
Purpose: Speckle-type POZ protein (SPOP) is important in DNA damage response (DDR) and maintenance of genomic stability. Somatic heterozygous missense mutations in the SPOP1 substrate-binding cleft are found in up to 15% of prostate cancers. While mutations in SPOP predict for benefit from androgen receptor signaling inhibition (ARSi) therapy, outcomes for patients with SPOP-mutant (SPOPmut) prostate cancer are heterogeneous and targeted treatments for SPOPmut castrate-resistant prostate cancer (CRPC) are lacking. Experimental Design: Using in silico genomic and transcriptomic tumor data, proteomics analysis and genetically modified cell line models we demonstrate mechanistic links between SPOP mutations, STING signaling alterations and PARP inhibitor vulnerabilities. Results: We demonstrate that SPOP mutations are associated with upregulation of a 29-gene non-canonical (NC) STING1 (NC-STING) signature in a subset of SPOPmut, treatment-refractory CRPC patients. We show in preclinical CRPC models that SPOP targets and destabilizes STING protein, and prostate cancer ̶ associated SPOP mutations result in upregulated NC-STING-NF-κB signaling and macrophage- and tumor microenvironment (TME)-facilitated reprogramming, leading to tumor cell growth. Importantly, we provide in vitro and in vivo mechanism-based evidence that PARP inhibitor (PARPi) treatment results in a shift from immunosuppressive NC-STING-NF-κB signaling to anti-tumor, canonical cGAS-STING-IFN-β signaling in SPOPmut CRPC and results in enhanced tumor growth inhibition. Conclusions: We provide evidence that SPOP is critical in regulating immunosuppressive versus anti-tumor activity downstream of DNA damage-induced STING activation in prostate cancer. PARPi treatment of SPOPmut CRPC alters this NC-STING signaling toward canonical, anti-tumor cGAS-STING-IFN-β signaling, highlighting a novel biomarker-informed treatment strategy for prostate cancer.
Supplementary Table S1 from Targeting Aggressive B-cell Lymphomas through Pharmacological Activation of the Mitochondrial Protease OMA1
Authors: Schwarzer Adrian , Oliveira Matheus , Kleppa Marc-Jens , Slattery Scott D. , Anantha Andy , Cooper Alan , Hannink Mark , Schambach Axel , Dörrie Anneke , Kotlyarov Alexey , Gaestel Matthias , Hembrough Todd , Levine Jedd , Luther Michael , Stocum Michael , Stiles Linsey , Weinstock David M. , Liesa Marc , Kostura Matthew J.
Published: November 2023

Results of Cell line screening data
Supplementary Figures 1 and 2 from Targeted Investigational Oncology Agents in the NCI-60: A Phenotypic Systems–based Resource
Authors: Morris Joel , Kunkel Mark W. , White Stephen L. , Wishka Donn G. , Lopez Omar D. , Bowles Lori , Sellers Brady Penny , Ramsey Patricia , Grams Julie , Rohrer Tiffany , Martin Karen , Dexheimer Thomas S. , Coussens Nathan P. , Evans David , Risbood Prabhakar , Sonkin Dmitriy , Williams John D. , Polley Eric C. , Collins Jerry M. , Doroshow James H. , Teicher Beverly A.
Published: November 2023

Figures S1 and S2
Supplementary Data from Targeted Nanofitin-drug Conjugates Achieve Efficient Tumor Delivery and Therapeutic Effect in an EGFRpos Mouse Xenograft Model
Authors: Huet Simon , Zeisser Labouebe Magali , Castro Rute , Jacquot Perrine , Pedrault Jessy , Viollet Sébastien , Van Simaeys Gaetan , Doumont Gilles , Larbanoix Lionel , Zindy Egor , Cunha António E. , Scapozza Leonardo , Cinier Mathieu
Published: November 2023

Figures S1 to S5
Supplementary Table S1 from Combination Therapies to Improve the Efficacy of Immunotherapy in Triple-negative Breast Cancer
Authors: Alečković Maša , Li Zheqi , Zhou Ningxuan , Qiu Xintao , Lulseged Bethlehem , Foidart Pierre , Huang Xiao-Yun , Garza Kodie , Shu Shaokun , Kesten Nikolas , Li Rong , Lim Klothilda , Garrido-Castro Ana C. , Guerriero Jennifer L. , Qi Jun , Long Henry W. , Polyak Kornelia
Published: November 2023

List of antibodies used.
Supplementary table S1 from Efficacy and Safety of Glycosphingolipid SSEA-4 Targeting CAR-T Cells in an Ovarian Carcinoma Model
Authors: Monzo Hector J. , Kalander Kerttu , Hyytiäinen Marko M. , Elbasani Endrit , Wall Johanna , Moyano-Galceran Lidia , Tanjore Ramanathan Jayendrakishore , Jukonen Joonas , Laakkonen Pirjo , Ristimäki Ari , Carlson Joseph W. , Lehti Kaisa , Salehi Sahar , Puolakkainen Pauli , Haglund Caj , Seppänen Hanna , Leppä Sirpa , Ojala Päivi M.
Published: November 2023

SSEA-4 expression in an ovarian cancer cohort.
Supplementary Figure S2 from Efficacy and Safety of Glycosphingolipid SSEA-4 Targeting CAR-T Cells in an Ovarian Carcinoma Model
Authors: Monzo Hector J. , Kalander Kerttu , Hyytiäinen Marko M. , Elbasani Endrit , Wall Johanna , Moyano-Galceran Lidia , Tanjore Ramanathan Jayendrakishore , Jukonen Joonas , Laakkonen Pirjo , Ristimäki Ari , Carlson Joseph W. , Lehti Kaisa , Salehi Sahar , Puolakkainen Pauli , Haglund Caj , Seppänen Hanna , Leppä Sirpa , Ojala Päivi M.
Published: November 2023

Supplementary Figure S2. Short-term in vivo study, dose-response, and weight monitoring. A. Treatment groups and used T cell doses. B. Weight monitoring in the indicated mice groups. CAR-T 3M treated mice showed a trend of mild weight loss. (M=1x106).
Data from Targeted Investigational Oncology Agents in the NCI-60: A Phenotypic Systems–based Resource
Authors: Morris Joel , Kunkel Mark W. , White Stephen L. , Wishka Donn G. , Lopez Omar D. , Bowles Lori , Sellers Brady Penny , Ramsey Patricia , Grams Julie , Rohrer Tiffany , Martin Karen , Dexheimer Thomas S. , Coussens Nathan P. , Evans David , Risbood Prabhakar , Sonkin Dmitriy , Williams John D. , Polley Eric C. , Collins Jerry M. , Doroshow James H. , Teicher Beverly A.
Published: November 2023

Abstract
The NCI-60 human tumor cell line panel has proved to be a useful tool for the global cancer research community in the search for novel chemotherapeutics. The publicly available cell line characterization and compound screening data from the NCI-60 assay have significantly contributed to the understanding of cellular mechanisms targeted by new oncology agents. Signature sensitivity/resistance patterns generated for a given chemotherapeutic agent against the NCI-60 panel have long served as fingerprint presentations that encompass target information and the mechanism of action associated with the tested agent. We report the establishment of a new public NCI-60 resource based on the cell line screening of a large and growing set of 175 FDA-approved oncology drugs (AOD) plus >825 clinical and investigational oncology agents (IOA), representing a diverse set (>250) of therapeutic targets and mechanisms. This data resource is available to the public (https://ioa.cancer.gov) and includes the raw data from the screening of the IOA and AOD collection along with an extensive set of visualization and analysis tools to allow for comparative study of individual test compounds and multiple compound sets.
Data from Targeted Nanofitin-drug Conjugates Achieve Efficient Tumor Delivery and Therapeutic Effect in an EGFRpos Mouse Xenograft Model
Authors: Huet Simon , Zeisser Labouebe Magali , Castro Rute , Jacquot Perrine , Pedrault Jessy , Viollet Sébastien , Van Simaeys Gaetan , Doumont Gilles , Larbanoix Lionel , Zindy Egor , Cunha António E. , Scapozza Leonardo , Cinier Mathieu
Published: November 2023

Abstract
Adjusting the molecular size, the valency and the pharmacokinetics of drug conjugates are as many leverages to improve their therapeutic window, notably by affecting tumor penetration, renal clearance, and short systemic exposure. In that regard, small tumor-targeting ligands are gaining attention. In this study, we demonstrate the benefits of the small Nanofitin alternative scaffolds (7 kDa) as selective tumor-targeting modules for the generation of drug conjugates, focusing on Nanofitins B10 and D8 directed against the EGFR. Owing to their small size and monovalent format, the two Nanofitins displayed a fast and deep tumor penetration in EGFR-positive A431 xenografts in BALB/c nude mice after intravenous administration, yielding to a targeting of respectively 67.9% ± 14.1 and 98.9% ± 0.7 of the tumor cells as demonstrated by IHC. Conjugation with the monomethyl auristatin E toxin provided homogeneous Nanofitin-drug conjugates, with an overall yield of ≥97%, for in vivo assessment in a curative xenograft model using bioluminescent, EGFR-positive, A431 cells in BALB/c nude mice. Internalization was found critical for efficient release of the toxin. Hence, the intravenous administration of the D8-based construct showed significant antitumor effect in vivo as determined by monitoring tumor volumes and bioluminescence levels over 2 months.
Data from Combination Therapies to Improve the Efficacy of Immunotherapy in Triple-negative Breast Cancer
Authors: Alečković Maša , Li Zheqi , Zhou Ningxuan , Qiu Xintao , Lulseged Bethlehem , Foidart Pierre , Huang Xiao-Yun , Garza Kodie , Shu Shaokun , Kesten Nikolas , Li Rong , Lim Klothilda , Garrido-Castro Ana C. , Guerriero Jennifer L. , Qi Jun , Long Henry W. , Polyak Kornelia
Published: November 2023

Abstract
Immune checkpoint inhibition combined with chemotherapy is currently approved as first-line treatment for patients with advanced PD-L1–positive triple-negative breast cancer (TNBC). However, a significant proportion of metastatic TNBC is PD-L1–negative and, in this population, chemotherapy alone largely remains the standard-of-care and novel therapeutic strategies are needed to improve clinical outcomes. Here, we describe a triple combination of anti-PD-L1 immune checkpoint blockade, epigenetic modulation thorough bromodomain and extra-terminal (BET) bromodomain inhibition (BBDI), and chemotherapy with paclitaxel that effectively inhibits both primary and metastatic tumor growth in two different syngeneic murine models of TNBC. Detailed cellular and molecular profiling of tumors from single and combination treatment arms revealed increased T- and B-cell infiltration and macrophage reprogramming from MHCIIlow to a MHCIIhigh phenotype in mice treated with triple combination. Triple combination also had a major impact on gene expression and chromatin profiles shifting cells to a more immunogenic and senescent state. Our results provide strong preclinical evidence to justify clinical testing of BBDI, paclitaxel, and immune checkpoint blockade combination.
Data from Preclinical development of brain permeable ERβ agonist for the treatment of glioblastoma
Authors: Pratap Uday P. , Tidwell Michael , Balinda Henriette U. , Clanton Nicholas A. , Yang Xue , Viswanadhapalli Suryavathi , Sareddy Gangadhara R. , Liang Dong , Xie Huan , Chen Yidong , Lai Zhao , Tekmal Rajeshwar R. , McHardy Stanton F. , Brenner Andrew J. , Vadlamudi Ratna K.
Published: November 2023

Abstract
Glioblastoma (GBM) is the most prevalent and aggressive type of adult brain tumors with low 5-year overall survival rates. Epidemiologic data suggest that estrogen may decrease brain tumor growth, and estrogen receptor beta (ERβ) has been demonstrated to exert anti-tumor functions in GBM. The lack of potent, selective and brain permeable ERβ agonist to promote its anti-tumor action is limiting the therapeutic promise of ERβ. In this study, we discovered that Indanone and tetralone-keto or hydroxyl oximes are a new class of ER agonists. Due to its high activity in ERβ reporter assays, specific binding to ERβ in polar screen assays, and potent growth inhibitory activity in GBM cells, CIDD-0149897 was discovered as a possible hit by screening a library of compounds. CIDD-0149897 is more selective for ERβ than ERα (40-fold). Treatment with CIDD-0149897 markedly reduced GBM cell viability with an IC50 of ~7-15 µM, while having little to no effect on ERβ-KO cells and normal human astrocytes. Further, CIDD-0149897 treatment enhanced expression of known ERβ target genes and promoted apoptosis in established and patient-derived GSC models. Pharmacokinetic studies confirmed that CIDD-0149897 has systemic exposure, and good bioavailability in the brain. Mice tolerated daily intraperitoneal treatment of CIDD-0149897 (50 mg/kg) with a 7-day repeat dosage with no toxicity. Additionally, CIDD-0149897 treatment significantly decreased tumor growth in U251 xenograft model and extended the survival of orthotopic GBM tumor-bearing mice. Collectively, these findings pointed to CIDD-0149897 as a new class of ERβ agonist, offering GBM patients a potential means of improving survival.
Supplementary Data File S1 from USP1 Expression Driven by EWS::FLI1 Transcription Factor Stabilizes Survivin and Mitigates Replication Stress in Ewing Sarcoma
Authors: Mallard Halle J. , Wan Shibiao , Nidhi Prakriti , Hanscom-Trofy Yvan D. , Mohapatra Bhopal , Woods Nicholas T. , Lopez-Guerrero Jose Antonio , Llombart-Bosch Antonio , Machado Isidro , Scotlandi Katia , Kreiling Natasha F. , Perry Megan C. , Mirza Sameer , Coulter Donald W. , Band Vimla , Band Hamid , Ghosal Gargi
Published: November 2023

RT-qPCR array of DUBs. RQ values of EWS cell lines normalized to GAPDH, represented as fold change relative to hMSC.
Figure S4 from USP1 Expression Driven by EWS::FLI1 Transcription Factor Stabilizes Survivin and Mitigates Replication Stress in Ewing Sarcoma
Authors: Mallard Halle J. , Wan Shibiao , Nidhi Prakriti , Hanscom-Trofy Yvan D. , Mohapatra Bhopal , Woods Nicholas T. , Lopez-Guerrero Jose Antonio , Llombart-Bosch Antonio , Machado Isidro , Scotlandi Katia , Kreiling Natasha F. , Perry Megan C. , Mirza Sameer , Coulter Donald W. , Band Vimla , Band Hamid , Ghosal Gargi
Published: November 2023

Figure S4 shows Identification of novel potential USP1 substrates.
Table S8 from CBF-Beta Mitigates PI3K-Alpha–Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: November 2023

Antibody dilutions for primary and secondary antibodies used
Table S4 from CBF-Beta Mitigates PI3K-Alpha–Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: November 2023

Z-transformed difference scores for each cell line as calculated from beta scores
Table S2 from CBF-Beta Mitigates PI3K-Alpha–Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: November 2023

Raw read counts for each guide RNA in screen
Table S6 from Stromal DDR2 Promotes Ovarian Cancer Metastasis through Regulation of Metabolism and Secretion of Extracellular Matrix Proteins
Authors: Schab Angela M. , Greenwade Molly M. , Stock Elizabeth , Lomonosova Elena , Cho Kevin , Grither Whitney R. , Noia Hollie , Wilke Daniel , Mullen Mary M. , Hagemann Andrea R. , Hagemann Ian S. , Thaker Premal H. , Kuroki Lindsay M. , McCourt Carolyn K. , Khabele Dineo , Powell Matthew A. , Mutch David G. , Zhao Peinan , Shriver Leah P. , Patti Gary J. , Longmore Gregory D. , Fuh Katherine C.
Published: November 2023

Cell line sequencing
Supplementary Figure 5 from Telomerase Upregulation Induces Progression of Mouse BrafV600E-Driven Thyroid Cancers and Triggers Nontelomeric Effects
Authors: Landa Iñigo , Thornton Caitlin E.M. , Xu Bin , Haase Jacob , Krishnamoorthy Gnana P. , Hao Jingzhu , Knauf Jeffrey A. , Herbert Zachary T. , Martínez Paula , Blasco María A. , Ghossein Ronald , Fagin James A.
Published: November 2023

In vivo dabrafenib plus trametinib treatment of mice.
Supplementary Figure 1 from Telomerase Upregulation Induces Progression of Mouse BrafV600E-Driven Thyroid Cancers and Triggers Nontelomeric Effects
Authors: Landa Iñigo , Thornton Caitlin E.M. , Xu Bin , Haase Jacob , Krishnamoorthy Gnana P. , Hao Jingzhu , Knauf Jeffrey A. , Herbert Zachary T. , Martínez Paula , Blasco María A. , Ghossein Ronald , Fagin James A.
Published: November 2023

Pairwise alignment of human:mouse telomerase reverse transcriptase (TERT) gene sequences.
Data from CBF-Beta Mitigates PI3K-Alpha–Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer
Authors: Stanland Lyla J. , Ang Hazel X. , Hoj Jacob P. , Chu Yunqiang , Tan Patrick , Wood Kris C. , Luftig Micah A.
Published: November 2023

Abstract
PIK3CA is the second most mutated gene in cancer leading to aberrant PI3K/AKT/mTOR signaling and increased translation, proliferation, and survival. Some 4%–25% of gastric cancers display activating PIK3CA mutations, including 80% of Epstein–Barr virus–associated GCs. Small molecules, including pan-PI3K and dual PI3K/mTOR inhibitors, have shown moderate success clinically, due to broad on-target/off-tissue effects. Thus, isoform-specific and mutant selective inhibitors have been of significant interest. However, drug resistance is a problem and has affected success of new drugs. There has been a concerted effort to define mechanisms of resistance and identify potent combinations in many tumor types, though gastric cancer is comparatively understudied. In this study, we identified modulators of the response to the PI3Kα-specific inhibitor, BYL719, in PIK3CA-mutant GCs. We found that loss of NEDD9 or inhibition of BCL-XL conferred hypersensitivity to BYL719, through increased cell-cycle arrest and cell death, respectively. In addition, we discovered that loss of CBFB conferred resistance to BYL719. CBFB loss led to upregulation of the protein kinase PIM1, which can phosphorylate and activate several overlapping downstream substrates as AKT thereby maintaining pathway activity in the presence of PI3Kα inhibition. The addition of a pan-PIM inhibitor re-sensitized resistant cells to BYL719. Our data provide clear mechanistic insights into PI3Kα inhibitor response in PIK3CA-mutant gastric tumors and can inform future work as mutant-selective inhibitors are in development for diverse tumor types.
Implications:
Loss of either NEDD9 or BCL-XL confers hypersensitivity to PI3K-alpha inhibition whereas loss of CBFB confers resistance through a CBFB/PIM1 signaling axis.
Data from Stromal DDR2 Promotes Ovarian Cancer Metastasis through Regulation of Metabolism and Secretion of Extracellular Matrix Proteins
Authors: Schab Angela M. , Greenwade Molly M. , Stock Elizabeth , Lomonosova Elena , Cho Kevin , Grither Whitney R. , Noia Hollie , Wilke Daniel , Mullen Mary M. , Hagemann Andrea R. , Hagemann Ian S. , Thaker Premal H. , Kuroki Lindsay M. , McCourt Carolyn K. , Khabele Dineo , Powell Matthew A. , Mutch David G. , Zhao Peinan , Shriver Leah P. , Patti Gary J. , Longmore Gregory D. , Fuh Katherine C.
Published: November 2023

Abstract
Ovarian cancer is the leading cause of gynecologic cancer–related deaths. The propensity for metastasis within the peritoneal cavity is a driving factor for the poor outcomes associated with this disease, but there is currently no effective therapy targeting metastasis. In this study, we investigate the contribution of stromal cells to ovarian cancer metastasis and identify normal stromal cell expression of the collagen receptor, discoidin domain receptor 2 (DDR2), that acts to facilitate ovarian cancer metastasis. In vivo, global genetic inactivation of Ddr2 impairs the ability of Ddr2-expressing syngeneic ovarian cancer cells to spread throughout the peritoneal cavity. Specifically, DDR2 expression in mesothelial cells lining the peritoneal cavity facilitates tumor cell attachment and clearance. Subsequently, omentum fibroblast expression of DDR2 promotes tumor cell invasion. Mechanistically, we find DDR2-expressing fibroblasts are more energetically active, such that DDR2 regulates glycolysis through AKT/SNAI1 leading to suppressed fructose-1,6-bisphosphatase and increased hexokinase activity, a key glycolytic enzyme. Upon inhibition of DDR2, we find decreased protein synthesis and secretion. Consequently, when DDR2 is inhibited, there is reduction in secreted extracellular matrix proteins important for metastasis. Specifically, we find that fibroblast DDR2 inhibition leads to decreased secretion of the collagen crosslinker, LOXL2. Adding back LOXL2 to DDR2 deficient fibroblasts rescues the ability of tumor cells to invade. Overall, our results suggest that stromal cell expression of DDR2 is an important mediator of ovarian cancer metastasis.
Implications:
DDR2 is highly expressed by stromal cells in ovarian cancer that can mediate metastasis and is a potential therapeutic target in ovarian cancer.
Table 2 from Polymorphisms in Cyclooxygenase, Lipoxygenase, and TP53 Genes Predict Colorectal Polyp Risk Reduction by Aspirin in the seAFOod Polyp Prevention Trial
Authors: Davies John R. , Mell Tracey , Fuller Harriett , Harland Mark , Saleh Rasha N.M. , Race Amanda D. , Rees Colin J. , Brown Louise C. , Loadman Paul M. , Downing Amy , Minihane Anne Marie , Williams Elizabeth A. , Hull Mark A.
Published: November 2023

SNP genotypes in PTGS genes that are associated with modification of the effect of aspirin on colorectal polyp number in the seAFOod polyp prevention trial.
Supplementary Figure 3 from Polymorphisms in Cyclooxygenase, Lipoxygenase, and TP53 Genes Predict Colorectal Polyp Risk Reduction by Aspirin in the seAFOod Polyp Prevention Trial
Authors: Davies John R. , Mell Tracey , Fuller Harriett , Harland Mark , Saleh Rasha N.M. , Race Amanda D. , Rees Colin J. , Brown Louise C. , Loadman Paul M. , Downing Amy , Minihane Anne Marie , Williams Elizabeth A. , Hull Mark A.
Published: November 2023

Supplementary Figure 3 shows the distribution of individual total (combined adenomatous and serrated polyp) colorectal polyp counts according to seAFOod trial treatment allocation by factorial margins and TP53 rs104522 genotype.
Data from MRTX1719 is an MTA-cooperative PRMT5 inhibitor that exhibits synthetic lethality in preclinical models and patients with MTAP deleted cancer
Authors: Engstrom Lars D. , Aranda Ruth , Waters Laura , Moya Krystal , Bowcut Vickie , Vegar Laura , Trinh David , Hebbert Allan , Smith Christopher R. , Kulyk Svitlana , Lawson J David. , He Leo , Hover Laura D. , Fernandez-Banet Julio , Hallin Jill , Vanderpool Darin , Briere David M. , Blaj Alice , Marx Matthew A. , Rodon Jordi , Offin Michael , Arbour Kathryn C. , Johnson Melissa L. , Kwiatkowski David J. , Janne Pasi A. , Haddox Candace L. , Papadopoulos Kyriakos P. , Henry Jason T. , Leventakos Konstantinos , Christensen James G. , Shazer Ronald , Olson Peter
Published: November 2023

Abstract
Previous studies implicated PRMT5 as a synthetic lethal target for MTAP deleted (MTAP del) cancers, however, the pharmacological characterization of small molecule inhibitors that recapitulate the synthetic lethal phenotype have not been described. MRTX1719 selectively inhibited PRMT5 in the presence of MTA, which is elevated in MTAP del cancers, and inhibited PRMT5-dependent activity and cell viability with >70-fold selectivity in HCT116 MTAP del compared to HCT116 MTAP WT cells. MRTX1719 demonstrated dose-dependent anti-tumor activity and inhibition of PRMT5-dependent SDMA modification in MTAP del tumors. In contrast, MRTX1719 demonstrated minimal effects on SDMA and viability in MTAP WT tumor xenografts, mouse or human hematopoietic cells. MRTX1719 demonstrated marked anti-tumor activity across a panel of xenograft models at well-tolerated doses. Early signs of clinical activity were observed including objective responses in patients with MTAP del melanoma, gallbladder adenocarcinoma, mesothelioma, non-small cell lung cancer, and MPNST from the Phase 1/2 study.
Airway Mucosal Remodeling: Mechanism of Action and Preclinical Data of Pulsed Electric Fields for Chronic Bronchitis and Mucus Hypersecretion
Authors: Krimsky William , Neal II Robert E. , Kim Victor
Published: November 2023

Patients living with chronic bronchitis (CB) suffer from physical limitations and poor quality of life. In general, treatment options that directly address the mucus hypersecretion component of CB are quite limited. Chronic airway inflammation and the associated hypersecretion and cough that are pathognomonic for CB generally result from long-term exposure to airway irritants such as tobacco use and other environmental insults. This, in turn, results in an increase in the quantity and change in composition of the airway mucosa as a consequence of altered goblet cells, club cells, and submucosal glands. Pulsed electric fields (PEFs) provide a method for eradicating the cellular constituents of tissue with limited impact on the stromal proteins. Preclinical evidence in porcine airways demonstrated that particular PEF waveforms allowed for salutary remodeling of the epithelial and submucosal airway tissue layers and appeared to foster rapid regeneration and recovery of the tissue. Therefore, a therapeutic opportunity might exist whereby the application of a specific form of PEF may result in a reduction of the cellular secretory constituents of the airway while also reducing airway mucosal inflammation. This review discusses the use of such PEF to address the underlying disease processes in CB including challenges around device design, dosing, and appropriate delivery methods. Further, we outline considerations for the transition to human airways along with a brief examination of the initial work treating CB patients, suggesting that the therapy is well tolerated with limited adverse events.
Amina : Representação de uma África pré-colonial entre Kannywood e Nollywood
Authors: Sani Ibrahima Kankara , Fonseca Mariana Bracks , Véras Bruno R.
Published: November 2023

Amina de Zazzau foi uma importante líder política e militar hauçá entre a virada do século XV e XVI. Este artigo tem como um de seus objetivos servir de subsídio e instrumento de apoio para debate sobre o filme Amina (2021), seja para leitura de estudantes de História e Humanidades em contexto universitário, ou professores de escola secundária utilizando o filme como instrumento didático. Para tanto este artigo se divide em três partes. Primeiramente discutiremos a produção audiovisual Amina (2021) no contexto regional e nacional da indústria cinematográfica nigeriana (Nollywood e Kannywood), como também a demanda proveniente de um nicho cosmopolita de consumo de audiovisual no mercado internacional de streaming para filmes africanos; segundo contextualizaremos a História de Amina, as fontes históricas sobre a personagem e contexto político e cultural do país Hauçá, notadamente o reino de Zazzau entre os séculos XV e XVI; por fim, discutiremos criticamente o filme em seus níveis narrativo e de produção, pensando as potencialidades didáticas do mesmo.
Sea Ice and Cloud Processes Mediating Compensation between Atmospheric and Oceanic Meridional Heat Transports across the CMIP6 Preindustrial Control Experiment
Authors: Kurtakoti Prajvala , Weijer Wilbert , Veneziani Milena , Rasch Philip J. , Verma Tarun
Published: November 2023

Bjerknes compensation (BJC) refers to the anticorrelation observed between atmospheric and oceanic heat transport (AHT/OHT) variability, particularly on decadal to longer time scales that may be important to the predictability of the climate system. This study investigates the spread in BJC across fully coupled simulations of phase 6 of the Coupled Model Intercomparison Project (CMIP6) and critical processes (particularly related to sea ice and clouds) that may contribute to that spread. BJC on decadal to longer time scales is confirmed across all the simulations evaluated, and it is strongest in the Northern Hemisphere (NH) between 60° and 70°N. At these latitudes, BJC appears to be primarily driven by the exchange of turbulent fluxes (sensible and latent) in the Greenland, Iceland, and Barents Seas. Metrics to break down how sea ice and clouds uniquely modify the radiative balance of the polar atmosphere during anomalous OHT events are presented. These metrics quantify the impacts of sea ice and clouds on surface and top of atmosphere (latent, sensible, longwave, and shortwave radiative) energy fluxes. Cloud responses tend to counter the clear sky impacts over the Marginal Ice Zone (MIZ). It is further shown that the degree of BJC present in a simulation at high latitudes is heavily influenced by the sensitivity of the sea ice to OHT, which is most influential over the MIZ. These results are qualitatively robust across models and explain the intermodel spread in NH BJC in the preindustrial control experiment.
An Observational, Irrigation-Sensitive Agricultural Drought Record from Weather Data
Authors: Tang Lois I. , McColl Kaighin A.
Published: November 2023

The historical rise of irrigation has profoundly mitigated the effect of drought on agriculture in many parts of the United States. While irrigation directly alters soil moisture, meteorological drought indices ignore the effects of irrigation, since they are often based on simple water balance models that neglect the irrigation input. Reanalyses also largely neglect irrigation. Other approaches estimate the evaporative fraction (EF), which is correlated with soil moisture under water-limited conditions typical of droughts, with lower values corresponding to drier soils. However, those approaches require satellite observations of land surface temperature, meaning they cannot be used to study droughts prior to the satellite era. Here, we use a recent theory of land–atmosphere coupling—surface flux equilibrium (SFE) theory—to estimate EF from readily available observations of near-surface air temperature and specific humidity with long historical records. In contrast to EF estimated from a reanalysis that largely neglects irrigation, the SFE-predicted EF is greater at irrigated sites than at nonirrigated sites during droughts, and its historical trends are typically consistent with the spatial distribution of irrigation growth. Two sites at which SFE-predicted EF unexpectedly rises in the absence of changes in irrigation can be explained by increased flooding due to human interventions unrelated to irrigation (river engineering and the expansion of fish hatcheries). This work introduces a new method for quantifying agricultural drought prior to the satellite era. It can be used to provide insight into the role of irrigation in mitigating drought in the United States over the twentieth century.

Significance Statement

Irrigation grew profoundly in the United States over the twentieth century, increasing the resilience of American agriculture to drought. Yet observational records of agricultural drought, and its response to irrigation, are limited to the satellite era. Here, we show that a common measure of agricultural drought (the evaporative fraction, EF) can be estimated using widespread weather data, extending the agricultural drought record decades further back in time. We show that EF estimated using our approach is both sensitive and specific to the occurrence of irrigation, unlike an alternative derived from a reanalysis.
To See or Not to See: Latinx (In)Visibility at a Newly Designated Hispanic-Serving Institution
Authors: Cox Jonathan M. , Stone Ashley , Vergara Angela , Carter Shannon K. , Carter J. Scott
Published: November 2023

More than two-thirds of Latinx undergraduate students in the U.S. obtain their college degrees from Hispanic-Serving Institutions (HSI), a designation based on the proportion of students who are of Latinx descent and low-income, instead of any federal guidelines for serving Latinx students. Existing literature identifies factors that aid students’ success at HSIs, but there is little knowledge about how Latinx students experience newly designated HSIs. This project centers the experiences of a sample of Latinx undergraduate students attending a newly designated HSI. Data consist of six focus group interviews with 23 students, focusing on participants’ decisions to attend the university and their experiences on campus. Data show students were attracted to the university with promotional materials portraying diversity and Latinx inclusion. However, they experienced the campus culture as promoting Latinx visibility in performative ways and among invisible workers, such as cleaning staff and groundskeepers. They found Latinx people and cultures to be largely invisible in the academic spaces of the university. Findings show how this mismatch between promotional materials and students’ experiences hinders their success and colors their experiences on campus.
Enterprise Content Management system implementation: Insights from the National Library and Archives of UAE
Authors: Chaterera-Zambuko Forget
Published: November 2023

This study aims to elucidate the key elements that contribute to the successful execution of an Enterprise Content Management (ECM) system. The insights provided are based on the experiences of professionals at the National Library and Archives of the United Arab Emirates (UAE) during their ECM implementation. An interpretive philosophical model, along with qualitative methodologies such as interviews and focus group discussions were employed for data collection. The participants included professionals from the UAE's National Library and Archives who played a significant role in the ECM system's implementation. A thorough review of relevant literature was also carried out to validate and reinforce the viewpoints obtained from the interviewees and focus group participants. The study discovered that comprehensive business needs assessment, detailed research, system compatibility, clarity of policies, and effective change management are vital for the successful roll-out of an ECM system. However, it's worth noting that the proposed implementation model offered in this study may not be all-encompassing. The insights shared are limited to the experiences of one archival institution, and the literature consulted may not cover all existing viewpoints. Despite these limitations, this research provides essential guidance, particularly to national archival institutions contemplating the adoption of ECM systems. It underlines the importance of ECM in effectively managing an organization's structured and unstructured data and emphasizes the need for due diligence during ECM implementation. Further research is recommended to explore the advantages arising from the successful implementation of an ECM system.
Non-linear analysis of the flexural-torsional stability of slender tropical glulam beams
Authors: Bikanda Louis Elvis , Lissouck René Oum , Massaga Morel Junior Angouah , Ohandja Louis Max Ayina
Published: November 2023

The main objective of this manuscript is to model the flexural-torsional buckling of slender tropical glulam beams using the finite element method. The non-linear approach to quantify both the buckling strength and the lateral geometrical features of wooden beams is proposed. A very rigorous methodology is used which is based on the kinematic Vlasov’s theory to determine the displacement field of the beam section by considering an updated Lagrangian description. For the finite element discretization, the Author develop a single wood element characterized by 14 degrees of freedom, i.e. seven degrees for each nodal point, and derive non-linear stiffness matrices by using the virtual works principle. The model is implemented in MatLab and the numerical results are compared with results based on the classical linear stability theory of slender wood beams. The selected case-studies are a cantilever beam and a beam on two supports.
Effects of biventricular shunt on pump characteristics in a maglev total artificial heart
Authors: Shida Shuya , Tsushima Kenichi , Osa Masahiro , Timms Daniel L , Masuzawa Toru
Published: November 2023

Severe left ventricular failure can progress to right ventricular failure, necessitating alternatives to heart transplantation, such as total artificial heart (TAH) treatment. Conventional TAHs encounter challenges associated with miniaturization and hemocompatibility owing to their reliance on mechanical valves and bearings. A magnetically levitated TAH (IB-Heart) was developed, utilizing a magnetic bearing. The IB-Heart features a distinctive biventricular shunt channel situated between the flow paths of the left and right centrifugal blood pumps, simplifying and miniaturizing its control system. However, the impact of these shunt channels remains underexplored. This study aimed to investigate the effects of shunt flow on pump characteristics and assess the IB-Heart’s potential to regulate flow balance between systemic and pulmonary circulation. At a rotational speed of 2000 rpm and flow rate range of 0–10 L/min, shunt flow exhibited a minor impact, with a 1.4 mmHg (1.3%) effect on pump characteristics. Shunt flow variation of about 0.13 L/min correlated with a 10 mmHg pressure difference between the pumps’ afterload and preload conditions. This variance was linked to changes in the inlet flow rates of the left and right pumps, signifying the ventricular shunt structure’s capacity to mirror the function of an atrial shunt in alleviating pulmonary congestion. The IB-Heart’s ventricular shunt structure enables passive regulation of left-right flow balance. The findings establish a fundamental technical groundwork for the development of IB-Hearts and TAHs with similar shunt structures. The innovative coupling of centrifugal pumps and the resultant effects on flow dynamics contribute to the advancement of TAH technology.
An innovative composite elbow manufacturing method with 6-axis robotic additive manufacturing for fabrication of complex composite structures
Authors: İpekçi Ahmet , Ekici Bülent
Published: November 2023

Filament winding method is the most commonly used method to produce profiles with different cross sections as composite product manufacturing. In this method, fiber material is wound with resin at different angles on a mold that has a suitable cross section shape. As a winding strategy, angled and helical winding can be done. Motion planning for this process is done with geodesic and nongeodesic theories. Requirement to use mold in the filament winding method increases the cost. Also, there is an obligation to helical windings. In winding of different layers, 90° angle cannot be given between the layers. To overcome all these constraints, UV curing can be achieved using photopolymer resin and continuous fiber glass fiber with the help of robotic additive manufacturing technology. Toolpath strategies for production has a key role in this work. As a tool path strategy, nonplanar slicing can be done and manufactured composite elbow in angular layers without mold. Then, under favour of 6-axis mobility of the industrial robot arm, layers can be obtained at exactly 90° angle. In addition, in this method, unlike other winding methods, internal voids, i.e. a filling rate, can be given within the cylindrical encircled layers. In order to verify whether the elbows produced with this method meet the requirements of the desired applications in the industry in terms of mechanical properties, at different filling rates (50%, 75%, 100%), winding turns (0 and 1/8), and different fiber densities (45%, 55% and 65%) 90° curved composite elbows were produced and their internal pressure strength tests were tested. Afterwards, an optimization study was carried out with the Taguchi method for the production parameters that will maximize the internal pressure strength. According to the results of the optimization study, it is seen that it is appropriate to choose the printing parameters that will obtain the highest internal pressure strength values for production with this method, 100% fill rate, 65% fiber density and 0° winding angle. The products made of this process have the advantage of easy-shaping, reasonable ratio of axial strength and encircled strength, specification easy-unifying, stable product quality.
Pseudoangiomatous Spindle Cell Lipoma: A Rare and Distinct Pattern of Lipomatous Tumors
Authors: Shaker Nada , Blankenship Heath , Shaker Nuha , Alhalaseh Yazan , Niu Shuo , Mansoor Ibrahim , Shakra Rafat Abu , Sangueza Omar P.
Published: November 2023

Pseudoangiomatous spindle cell lipoma is a rare pattern within the spindle cell lipoma spectrum that exhibits a remarkable histological pattern characterized by its resemblance to vascular lesions, creating a pseudoangiomatous appearance. Approximately 20 to 30 reports have been described in the literature. In this context, we present an intriguing report of pseudoangiomatous spindle cell lipoma showcasing a unique low-fat pseudo angiomatous pattern in a 61-year-old male patient presented with a 6-cm subcutaneous mass on his right arm, which was thoroughly investigated and subsequently excised. Microscopic examination revealed bland spindle cells infiltrates within a fibromyxoid stroma. Notably, the tumor exhibited distinctive branching and dilated vascular-like spaces that formed pseudopapillary (villiform) projections. Interestingly, the tumor displayed certain regions featuring mature adipose tissue components, alongside hyalinized blood vessels. No necrosis, atypical spindle cells, increased mitotic activity, or pleomorphic lipoblasts were observed. The immunohistochemical evaluation demonstrated diffuse positive staining for CD34 and negative staining for STAT6. This report of a low-fat pattern of pseudoangiomatous spindle cell lipoma underscores the importance of recognizing and characterizing rare entity subtype for accurate diagnosis and appropriate management. This report contributes to the expanding understanding of the diverse presentations of pseudo angiomatous spindle cell lipomas and underscores the significance of comprehensive histopathological assessment.
Brachial plexus block using only 1% lidocaine to reduce pain during the endovascular treatment of dysfunctional arteriovenous access
Authors: Park Sung-Joon , Chung Hwan Hoon , Lee Yun Hak , Lee Hyoung Nam , Cho Youngjong , Lee Sangjoon , Lee Seung Hwa , Yang Woo Young
Published: November 2023

Background:

Interventional endovascular treatments of dysfunctional arteriovenous (AV) access for hemodialysis can cause pain and discomfort to the patients. Ultrasound-guided brachial plexus block (BPB) is an alternative regional anesthesia method, but conventional BPB using ropivacaine or bupivacaine may cause long-lasting motor power loss, significantly reducing patient satisfaction. This study aimed to introduce BPB using only 1% lidocaine, which induces sensory loss while minimizing motor block, and evaluate the efficacy and safety of this procedure.

Methods:

This retrospective study was conducted on 277 consecutive patients with dysfunctional AV access requiring percutaneous transluminal angioplasty (PTA). Of these, 174 patients underwent the BPB procedure using 1% lidocaine. Time data were recorded, and the motor strength grade (MRC scale, grade 0–5) was evaluated. Numeric rating pain score (NRPS, grade 0–10) was asked during every PTA, and overall NRPS and satisfaction scores (scale 1–3) were asked after the procedure was completed.

Results:

Of the 174 patients who received BPB, the success rate was 100%, and there were no significant complications related to BPB. The MRC scale measured at the time when the complete sensory loss was achieved was 1.99 ± 0.63, and that at the point of sensory recovery when the block effect expired was 3.93 ± 0.62, indicating a good grade of motor strength. The average NRPS during PTA in the BPB group was significantly lower than that of the control group without BPB (1.04 ± 2.04vs 6.30 ± 2.71, p < 0.001). The overall satisfaction score was significantly higher in the BPB group than in the control group (2.79 ± 0.50vs 2.00 ± 0.81, p < 0.001).

Conclusions:

BPB using only 1% lidocaine can induce a sensory block while minimizing the effect on motor function. It can be applied safely in an outpatient clinic setting with relatively higher satisfaction.
Do we have the right to call ourselves an inclusive university? Untold stories of queer students at a rural university in Eastern Cape Province, South Africa
Authors: Banda Chitsamatanga Bellita
Published: November 2023

Ruraqueer students constantly experience higher levels of victimization, and negative university experiences than their urban and suburban peers. Further, rural students have limited access to university resources while, queer events and workshops related to queer community, as well as university-based ongoing activities to support positive sexuality and gender identity development are scanty. This has been worsened by extant research written from an ‘outsider’ perspective lacking breadth and depth of experiences of queer students especially in rural universities from an African perspective. Anchored on a qualitative approach using purposive sampling, in depth semi-structured interviews were conducted in this study with eight under and postgraduate students who identified as queer. Emerging themes show how rurality intersects with actual or perceived sexual orientation, gender identity or sex characteristics of queer students in university spaces. Findings challenge the homogenization of university residencies; non-inclusive LGBTQ curricular; university environment that remains homophobic and how traditional, cultural and societal norms contribute to queer students sense of belonging. Implications suggest inclusive teaching and learning and ongoing awareness programmes that acknowledge diversity and enhance visibility of students with intersecting marginalized identities.
Stretchy and Tense: A Diffractive Auto/Ethnography of Privilege With Yoga Pants
Authors: McKibben Elizabeth
Published: November 2023

The contemporary yoga industry is entangled in many contradictions. While yoga is intended to be an inclusive, liberatory practice, its contemporary iterations enact exclusion through an industry that often privileges able-bodied, affluent, white women. As a yoga scholar-practitioner who embodies these identities, I am troubled by how my teaching and studies of yoga further replicate power imbalances. In this article, I interrogate privilege and power as they emerge with yoga pants. I draw upon Barad’s cutting together-apart in a diffractive auto/ethnography. I make literal cuts through the fabric of my yoga pants, as reflections, reactions, and interview transcripts make figurative cuts through self-image, body-image, and feminine norms. I consider how this methodology materializes an entanglement of affective forces, power, and critical feminist academia that is useful in exploring possibilities for change. This inquiry does not conclude, but rather acknowledges an imperfect and ever-evolving interrogation of embodied power as it shapes intellectual inquiry, and spaces of yoga practice.