bluuebunny/crossref_metadata_2025 huggingface dataset:
A Phase I First-in-Human Study of ABBV-011, a Seizure-Related Homolog Protein 6–Targeting Antibody–Drug Conjugate, in Patients with Small Cell Lung Cancer
Authors: Morgensztern Daniel , Ready Neal , Johnson Melissa L. , Dowlati Afshin , Choudhury Noura , Carbone David P. , Schaefer Eric , Arnold Susanne M. , Puri Sonam , Piotrowska Zofia , Hegde Aparna , Chiang Anne C. , Iams Wade , Tolcher Anthony , Nosaki Kaname , Kozuki Toshiyuki , Li Tianhong , Santana-Davila Rafael , Akamatsu Hiroaki , Murakami Haruyasu , Yokouchi Hiroshi , Wang Song , Zha Jiuhong , Li Rui , Robinson Randy R. , Hingorani Pooja , Jeng Edwin E. , Furqan Muhammad
Published: September 2024

Purpose:

Seizure-related homolog protein 6 (SEZ6) is a novel target expressed in small cell lung cancer (SCLC). ABBV-011, a SEZ6-targeted antibody conjugated to calicheamicin, was evaluated in a phase I study (NCT03639194) in patients with relapsed/refractory SCLC. We report initial outcomes of ABBV-011 monotherapy.

Patients and Methods:

ABBV-011 was administered intravenously once every 3 weeks during dose escalation (0.3–2 mg/kg) and expansion. Patients with SEZ6-positive tumors (≥25% of tumor cells with ≥1+ staining intensity by IHC) were preselected for expansion. Safety, tolerability, antitumor activity, and pharmacokinetics were evaluated.

Results:

As of August 2022, 99 patients received ABBV-011 monotherapy [dose escalation, n = 36; Japanese dose evaluation, n = 3; dose expansion, n = 60 (1 mg/kg, n = 40)]; the median age was 63 years (range, 41–79 years). Also, 32%, 41%, and 26% of patients received 1, 2, and ≥3 prior therapies, respectively. The maximum tolerated dose was not reached through 2.0 mg/kg. The most common treatment-emergent adverse events were fatigue (50%), nausea (42%), and thrombocytopenia (41%). The most common hepatic treatment-emergent adverse events were increased aspartate aminotransferase (22%), increased γ-glutamyltransferase (21%), and hyperbilirubinemia (17%); two patients experienced veno-occlusive liver disease. The objective response rate was 19% (19/98). In the 1-mg/kg dose-expansion cohort (n = 40), the objective response rate was 25%; the median response duration was 4.2 months (95% confidence interval, 2.6–6.7); and the median progression-free survival was 3.5 months (95% confidence interval, 1.5–4.2).

Conclusions:

ABBV-011 1.0 mg/kg every 3 weeks monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated patients with relapsed/refractory SCLC. SEZ6 is a promising novel SCLC target and warrants further investigation.
Cancer in Multilineage Mosaic RASopathies due to Pathogenic Variants in HRAS or KRAS: A Systematic Review and Meta-analysis
Authors: Windrich Jonas , Ney Gina M. , Rosenberg Philip S. , Kim Jung , Zenker Martin , Stewart Douglas R. , Kratz Christian P.
Published: September 2024

Purpose:

To determine the cancer risk and spectrum in patients with multilineage mosaic RASopathies with pathogenic variants (PV) in HRAS or KRAS.

Experimental Design:

We conducted a systematic literature review to identify multilineage mosaic RASopathy cases with a PV in HRAS or KRAS to create a retrospective cohort. We calculated cumulative incidence, cancer-free survival, and hazard rates for cancer and standardized incidence rates (SIR).

Results:

This study identified 69 patients. Of these, 17% had cancer, including rhabdomyosarcoma (RMS) located in the urogenital region (n = 7), skin cancer (n = 3), Wilms tumor (n = 1), and bladder cancer (n = 1). Cumulative cancer incidence by age 20 was 20% (95% confidence interval, 4%–37%). The annual cancer hazard rate peaked at 14% within the first 2 years of life. The highest SIR was found for RMS (SIR = 800; 95% confidence interval, 300–1648).

Conclusions:

This is the first investigation of cancer risk in KRAS or HRAS PV–positive mosaic RASopathies to date. The high incidence and SIR values found highlight the need for rigorous RMS surveillance in young children and skin cancer surveillance in adults with this high-risk condition.
Figure 8 from N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma
Authors: Geroyska Sofia , Mejia Isabel , Chan Alfred A. , Navarrete Marian , Pandey Vijaya , Kharpatin Samuel , Noguti Juliana , Wang Feng , Srole Daniel , Chou Tsui-Fen , Wohlschlegel James , Nemeth Elizabeta , Damoiseaux Robert , Shackelford David B. , Lee Delphine J. , Díaz Begoña
Published: September 2024

Genetic targeting of TIM17A causes mitochondrial ferrous iron accumulation and activation of parthanatos in (KL/K)MUT lung carcinoma cells. A, Mitochondrial ferrous iron detection in (KL/K)MUT and (KL/K)WT cells transfected with non-targeting control or two different TIM17A siRNAs. Quantification of signal intensity on a representative experiment out of two using randomly imaged fields containing at least 480 cells per experimental condition. Graph bars, group mean; error bars, SEM. a.u., arbitrary units. *, P = 0.0101 for control vs. #1, P = 0.0131 for control vs. #2; ns = not significant (Student t test). Representative microscope images are shown. Arrowheads, Mito-FerroGreen positive cells. Bars, 15 μm. Bottom, TIM17A immunoblotting in lysates from the cells used above. Numbers: band intensity normalized to actin control. B, Protein PARylation detection by immunoblotting in H1792 cells transfected with non-targeting control and two different TIM17A oligos for 72 hours. Numbers: band intensity normalized to actin control. C, H460 cells stably expressing a Tet-inducible TIM17A shRNA treated or not with Dox were stained with p-H2A.X and DAPI. Arrowheads, nuclei containing p-H2A.X-positive foci. Bar, 10 μm. D, AIF subcellular localization in (KL/K)MUT H460 cells stably expressing a Tet-inducible TIM17A shRNA treated or not with Dox. Cytoplasmic and nuclear lysates were separated and immunoblotted for AIF. Tubulin, TOM20, and lamin staining were used to verify fraction purity. Numbers: nuclear AIF band intensity normalized to lamin A/B. E, Summary of our findings reporting that myristoylation inhibition induces parthanatos through loss of TIM17A and mitochondrial ferrous iron overload in (KL/K)MUT lung carcinoma.
Supplementary Table 3 from A Pilot Study of the CD38 Antagonist Daratumumab in Patients with Metastatic Renal Cell Carcinoma or Muscle-Invasive Bladder Cancer
Authors: Campbell Matthew T. , Shah Amishi Y. , Msaouel Pavlos , Tannir Nizar M. , Siefker-Radtke Arlene O. , Kamat Ashish M. , Navai Neema , Dinney Colin P.N. , Rao Priya , Guo Charles C. , Sheth Rahul A. , Venkatesan Aradhana M. , Tidwell Rebecca S. , Yadav Shalini S. , Gu Aidi , Chen Hong , Macaluso Marc , Duan Fei , Basu Sreyashi , Jindal Sonali , Sharma Padmanee
Published: September 2024

All Adverse Events in the MIBC cohort regardless of attribution
Supplementary Figure 3 from A Pilot Study of the CD38 Antagonist Daratumumab in Patients with Metastatic Renal Cell Carcinoma or Muscle-Invasive Bladder Cancer
Authors: Campbell Matthew T. , Shah Amishi Y. , Msaouel Pavlos , Tannir Nizar M. , Siefker-Radtke Arlene O. , Kamat Ashish M. , Navai Neema , Dinney Colin P.N. , Rao Priya , Guo Charles C. , Sheth Rahul A. , Venkatesan Aradhana M. , Tidwell Rebecca S. , Yadav Shalini S. , Gu Aidi , Chen Hong , Macaluso Marc , Duan Fei , Basu Sreyashi , Jindal Sonali , Sharma Padmanee
Published: September 2024

Kaplan Meier curves in renal cohort A) Overall Survival and B) Progression Free Survival (PFS)
Supplementary Table 1 from Inhibition of Notch4 Using Novel Neutralizing Antibodies Reduces Tumor Growth in Murine Cancer Models by Targeting the Tumor Endothelium
Authors: Eng Jason W.-L. , Kato Yu , Adachi Yusuke , Swaminathan Bhairavi , Naiche L.A. , Vadakath Rahul , Sakamoto Yoshimasa , Nakazawa Youya , Tachino Sho , Ito Ken , Abe Takanori , Minoshima Yukinori , Hoshino-Negishi Kana , Ogasawara Hideaki , Kawakatsu Tomomi , Nishimura Miyuki , Katayama Masahiko , Shimizu Masashi , Tahara Kazuhiro , Sato Toshitaka , Suzuki Katsuhisa , Agarwala Kishan , Iwata Masao , Nomoto Kenichi , Ozawa Yoichi , Imai Toshio , Funahashi Yasuhiro , Matsui Junji , Kitajewski Jan
Published: September 2024

List of constructs developed and used for experiments including Notch 1-4 expression constructs and the Notch luciferase reporter construct.
Figure S6 from N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma
Authors: Geroyska Sofia , Mejia Isabel , Chan Alfred A. , Navarrete Marian , Pandey Vijaya , Kharpatin Samuel , Noguti Juliana , Wang Feng , Srole Daniel , Chou Tsui-Fen , Wohlschlegel James , Nemeth Elizabeta , Damoiseaux Robert , Shackelford David B. , Lee Delphine J. , Díaz Begoña
Published: September 2024

Inhibition of NMT prevents cell cycle progression and causes death in lung carcinoma cells.
Table S4 from E2F1-Associated Purine Synthesis Pathway Is a Major Component of the MET-DNA Damage Response Network
Authors: Poliaková Turan Michaela , Riedo Rahel , Medo Matúš , Pozzato Chiara , Friese-Hamim Manja , Koch Jonas P. , Coggins Si’Ana A. , Li Qun , Kim Baek , Albers Joachim , Aebersold Daniel M. , Zamboni Nicola , Zimmer Yitzhak , Medová Michaela
Published: September 2024

Summary of the significance analysis for the survival analyses.
Figure S11 from N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma
Authors: Geroyska Sofia , Mejia Isabel , Chan Alfred A. , Navarrete Marian , Pandey Vijaya , Kharpatin Samuel , Noguti Juliana , Wang Feng , Srole Daniel , Chou Tsui-Fen , Wohlschlegel James , Nemeth Elizabeta , Damoiseaux Robert , Shackelford David B. , Lee Delphine J. , Díaz Begoña
Published: September 2024

Effect of NMTi on the abundance of TIM17A in lung carcinoma cells.
Figure S1 from N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma
Authors: Geroyska Sofia , Mejia Isabel , Chan Alfred A. , Navarrete Marian , Pandey Vijaya , Kharpatin Samuel , Noguti Juliana , Wang Feng , Srole Daniel , Chou Tsui-Fen , Wohlschlegel James , Nemeth Elizabeta , Damoiseaux Robert , Shackelford David B. , Lee Delphine J. , Díaz Begoña
Published: September 2024

NMT1 is a therapeutic target in lung carcinoma
Supplementary Table 8 from Spatial Landscape of Malignant Pleural and Peritoneal Mesothelioma Tumor Immune Microenvironments
Authors: Ma Xiaojun , Lembersky David , Kim Elena S. , Becich Michael J. , Testa Joseph R. , Bruno Tullia C. , Osmanbeyoglu Hatice U.
Published: September 2024

Comparison of cell–cell contact score differences between malignant pleural mesothelioma (MPM) and malignant peritoneal mesothelioma (MPeM).
Supplementary Table 7 from Spatial Landscape of Malignant Pleural and Peritoneal Mesothelioma Tumor Immune Microenvironments
Authors: Ma Xiaojun , Lembersky David , Kim Elena S. , Becich Michael J. , Testa Joseph R. , Bruno Tullia C. , Osmanbeyoglu Hatice U.
Published: September 2024

Comparison of clinical parameters between malignant pleural mesothelioma (MPM) and malignant peritoneal mesothelioma (MPeM) for various cell types.
Supplementary Table 3 from Spatial Landscape of Malignant Pleural and Peritoneal Mesothelioma Tumor Immune Microenvironments
Authors: Ma Xiaojun , Lembersky David , Kim Elena S. , Becich Michael J. , Testa Joseph R. , Bruno Tullia C. , Osmanbeyoglu Hatice U.
Published: September 2024

Comparison of differences in cell–cell contact scores between malignant pleural mesothelioma (MPM) and malignant peritoneal mesothelioma (MPeM) tumors.
Supplementary Table 2 from Spatial Landscape of Malignant Pleural and Peritoneal Mesothelioma Tumor Immune Microenvironments
Authors: Ma Xiaojun , Lembersky David , Kim Elena S. , Becich Michael J. , Testa Joseph R. , Bruno Tullia C. , Osmanbeyoglu Hatice U.
Published: September 2024

Clinical features, cell count, tumor percentage, and density associated with each core, including marker percentage, density and intensity for each core.
Figure S2 from Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma
Authors: Iwanaga Ritsuko , Yamamoto Tomomi M. , Gomez Karina , Nguyen Lily L. , Woodruff Elizabeth R. , Post Miriam D. , Mikeska Railey G. , Danis Etienne , Danhorn Thomas , Boorgula Meher P. , Mitra Siddhartha S. , Marjon Nicole A. , Bitler Benjamin G. , Brubaker Lindsay W.
Published: September 2024

CBX2 expression associates with epithelial state 6. CBX2 protein expression does not correlate with T cell infiltration. CXCL1, 5, and CXCL8 expression correlation with Macrophage M0_CIBERSORT infiltration.
Figure S1 from Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma
Authors: Iwanaga Ritsuko , Yamamoto Tomomi M. , Gomez Karina , Nguyen Lily L. , Woodruff Elizabeth R. , Post Miriam D. , Mikeska Railey G. , Danis Etienne , Danhorn Thomas , Boorgula Meher P. , Mitra Siddhartha S. , Marjon Nicole A. , Bitler Benjamin G. , Brubaker Lindsay W.
Published: September 2024

CBX2 binds to promoter regions of cytokine genes and CBX2 is significantly associated with immune signatures.
Supplementary Figure 3 from IFNγ Production by Functionally Reprogrammed Tregs Promotes Antitumor Efficacy of OX40/CD137 Bispecific Agonist Therapy
Authors: Imianowski Charlotte J. , Kuo Paula , Whiteside Sarah K. , von Linde Teresa , Wesolowski Alexander J. , Conti Alberto G. , Evans Alexander C. , Baird Tarrion , Morris Benjamin I. , Fletcher Nicole E. , Yang Jie , Poon Edmund , Lakins Matthew A. , Yamamoto Masahiro , Brewis Neil , Morrow Michelle , Roychoudhuri Rahul
Published: September 2024

Supplementary Figure 3: Increased IL-2 expression by conventional CD4+ and CD8+ T cells with FS120m treatment. Representative plots (left) and replicate measurements (right) of IL-2+ CD4+ Tconv cells and CD8+ T cells in the spleen and draining lymph nodes on day 18 post tumor implantation. *** P ≤ 0.001, **** P ≤ 0.0001. Unpaired Student’s t test. Bars and error are mean and s.e.m.
Supplementary Figure 1 from IFNγ Production by Functionally Reprogrammed Tregs Promotes Antitumor Efficacy of OX40/CD137 Bispecific Agonist Therapy
Authors: Imianowski Charlotte J. , Kuo Paula , Whiteside Sarah K. , von Linde Teresa , Wesolowski Alexander J. , Conti Alberto G. , Evans Alexander C. , Baird Tarrion , Morris Benjamin I. , Fletcher Nicole E. , Yang Jie , Poon Edmund , Lakins Matthew A. , Yamamoto Masahiro , Brewis Neil , Morrow Michelle , Roychoudhuri Rahul
Published: September 2024

Supplementary Figure 1: OX40 and CD137 are highly expressed on Treg cells. Representative plots showing OX40+ (left) and CD137+ (right) SP resting or activated cells from the spleen and tumor on day 18 post tumor implantation. ** P ≤ 0.01, *** P ≤ 0.001, **** P ≤ 0.0001. One-way ANOVA with Tukey’s correction for multiple comparisons. Bars and error are mean and s.e.m.
Data from N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma
Authors: Geroyska Sofia , Mejia Isabel , Chan Alfred A. , Navarrete Marian , Pandey Vijaya , Kharpatin Samuel , Noguti Juliana , Wang Feng , Srole Daniel , Chou Tsui-Fen , Wohlschlegel James , Nemeth Elizabeta , Damoiseaux Robert , Shackelford David B. , Lee Delphine J. , Díaz Begoña
Published: September 2024

Abstract
Myristoylation is a type of protein acylation by which the fatty acid myristate is added to the N-terminus of target proteins, a process mediated by N-myristoyltransferases (NMT). Myristoylation is emerging as a promising cancer therapeutic target; however, the molecular determinants of sensitivity to NMT inhibition or the mechanism by which it induces cancer cell death are not completely understood. We report that NMTs are a novel therapeutic target in lung carcinoma cells with LKB1 and/or KEAP1 mutations in a KRAS-mutant background. Inhibition of myristoylation decreases cell viability in vitro and tumor growth in vivo. Inhibition of myristoylation causes mitochondrial ferrous iron overload, oxidative stress, elevated protein poly (ADP)-ribosylation, and death by parthanatos. Furthermore, NMT inhibitors sensitized lung carcinoma cells to platinum-based chemotherapy. Unexpectedly, the mitochondrial transporter translocase of inner mitochondrial membrane 17 homolog A (TIM17A) is a critical target of myristoylation inhibitors in these cells. TIM17A silencing recapitulated the effects of NMT inhibition at inducing mitochondrial ferrous iron overload and parthanatos. Furthermore, sensitivity of lung carcinoma cells to myristoylation inhibition correlated with their dependency on TIM17A. This study reveals the unexpected connection between protein myristoylation, the mitochondrial import machinery, and iron homeostasis. It also uncovers myristoylation inhibitors as novel inducers of parthanatos in cancer, and the novel axis NMT-TIM17A as a potential therapeutic target in highly aggressive lung carcinomas.
Significance:
KRAS-mutant lung carcinomas with LKB1 and/or KEAP1 co-mutations have intrinsic therapeutic resistance. We show that these tumors are sensitive to NMT inhibitors, which slow tumor growth in vivo and sensitize cells to platinum-based chemotherapy in vitro. Inhibition of myristoylation causes death by parthanatos and thus has the potential to kill apoptosis and ferroptosis-resistant cancer cells. Our findings warrant investigation of NMT as a therapeutic target in highly aggressive lung carcinomas.
Data from E2F1-Associated Purine Synthesis Pathway Is a Major Component of the MET-DNA Damage Response Network
Authors: Poliaková Turan Michaela , Riedo Rahel , Medo Matúš , Pozzato Chiara , Friese-Hamim Manja , Koch Jonas P. , Coggins Si’Ana A. , Li Qun , Kim Baek , Albers Joachim , Aebersold Daniel M. , Zamboni Nicola , Zimmer Yitzhak , Medová Michaela
Published: September 2024

Abstract
Various lines of investigation support a signaling interphase shared by receptor tyrosine kinases and the DNA damage response. However, the underlying network nodes and their contribution to the maintenance of DNA integrity remain unknown. We explored MET-related metabolic pathways in which interruption compromises proper resolution of DNA damage. Discovery metabolomics combined with transcriptomics identified changes in pathways relevant to DNA repair following MET inhibition (METi). METi by tepotinib was associated with the formation of γH2AX foci and with significant alterations in major metabolic circuits such as glycolysis, gluconeogenesis, and purine, pyrimidine, amino acid, and lipid metabolism. 5′-Phosphoribosyl-N-formylglycinamide, a de novo purine synthesis pathway metabolite, was consistently decreased in in vitro and in vivo MET-dependent models, and METi-related depletion of dNTPs was observed. METi instigated the downregulation of critical purine synthesis enzymes including phosphoribosylglycinamide formyltransferase, which catalyzes 5′-phosphoribosyl-N-formylglycinamide synthesis. Genes encoding these enzymes are regulated through E2F1, whose levels decrease upon METi in MET-driven cells and xenografts. Transient E2F1 overexpression prevented dNTP depletion and the concomitant METi-associated DNA damage in MET-driven cells. We conclude that DNA damage following METi results from dNTP reduction via downregulation of E2F1 and a consequent decline of de novo purine synthesis.
Significance:
Maintenance of genome stability prevents disease and affiliates with growth factor receptor tyrosine kinases. We identified de novo purine synthesis as a pathway in which key enzymatic players are regulated through MET receptor and whose depletion via MET targeting explains MET inhibition-associated formation of DNA double-strand breaks. The mechanistic importance of MET inhibition-dependent E2F1 downregulation for interference with DNA integrity has translational implications for MET-targeting-based treatment of malignancies.
Data from Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma
Authors: Iwanaga Ritsuko , Yamamoto Tomomi M. , Gomez Karina , Nguyen Lily L. , Woodruff Elizabeth R. , Post Miriam D. , Mikeska Railey G. , Danis Etienne , Danhorn Thomas , Boorgula Meher P. , Mitra Siddhartha S. , Marjon Nicole A. , Bitler Benjamin G. , Brubaker Lindsay W.
Published: September 2024

Abstract
Chromobox 2 (CBX2), an epigenetic reader and component of polycomb repressor complex 1, is highly expressed in >75% of high-grade serous carcinoma. Increased CBX2 expression is associated with poorer survival, whereas CBX2 knockdown leads to improved chemotherapy sensitivity. In a high-grade serous carcinoma immune-competent murine model, knockdown of CBX2 decreased tumor progression. We sought to explore the impact of modulation of CBX2 on the tumor immune microenvironment (TIME), understanding that the TIME plays a critical role in disease progression and development of therapy resistance. Exploration of existing datasets demonstrated that elevated CBX2 expression significantly correlated with specific immune cell types in the TIME. RNA sequencing and pathway analysis of differentially expressed genes demonstrated immune signature enrichment. Confocal microscopy and co-culture experiments found that modulation of CBX2 leads to increased recruitment and infiltration of macrophages. Flow cytometry of macrophages cultured with CBX2-overexpressing cells showed increased M2-like macrophages and decreased phagocytosis activity. Cbx2 knockdown in the Trp53-null, Brca2-null ID8 syngeneic murine model (ID8 Trp53−/−Brca2−/−) led to decreased tumor progression compared with the control. NanoString immuno-oncology panel analysis suggested that knockdown in Cbx2 shifts immune cell composition, with an increase in macrophages. Multispectral immunohistochemistry (mIHC) further confirmed an increase in macrophage infiltration. Increased CBX2 expression leads to recruitment and polarization of protumor macrophages, and targeting CBX2 may serve to modulate the TIME to enhance the efficacy of immune therapies.
Significance:
CBX2 expression correlates with the TIME. CBX2 modulation shifts the macrophage population, potentially leading to an immunosuppressive microenvironment, highlighting CBX2 as a target to improve efficacy of immunotherapy.
Chemotherapy Enriches for Proinflammatory Macrophage Phenotypes that Support Cancer Stem-Like Cells and Disease Progression in Ovarian Cancer
Authors: Cruz Luisjesus S. , Robinson Mikella , Stevenson Denay , Amador Isabella C. , Jordan Gregory J. , Valencia Sofia , Navarrete Carolina , House Carrie D.
Published: September 2024

High-grade serous ovarian cancer remains a poorly understood disease with a high mortality rate. Although most patients respond to cytotoxic therapies, a majority will experience recurrence. This may be due to a minority of drug-resistant cancer stem-like cells (CSC) that survive chemotherapy and are capable of repopulating heterogeneous tumors. It remains unclear how CSCs are supported in the tumor microenvironment (TME) particularly during chemotherapy exposure. Tumor-associated macrophages (TAM) make up half of the immune population of the ovarian TME and are known to support CSCs and contribute to cancer progression. TAMs are plastic cells that alter their phenotype in response to environmental stimuli and thus may influence CSC maintenance during chemotherapy. Given the plasticity of TAMs, we studied the effects of carboplatin on macrophage phenotypes using both THP1- and peripheral blood mononuclear cell (PBMC)–derived macrophages and whether this supports CSCs and ovarian cancer progression following treatment. We found that carboplatin exposure induces an M1-like proinflammatory phenotype that promotes SOX2 expression, spheroid formation, and CD117+ ovarian CSCs, and that macrophage-secreted CCL2/MCP-1 is at least partially responsible for this effect. Depletion of TAMs during carboplatin exposure results in fewer CSCs and prolonged survival in a xenograft model of ovarian cancer. This study supports a role for platinum-based chemotherapies in promoting a transient proinflammatory M1-like TAM that enriches for CSCs during treatment. Improving our understanding of TME responses to cytotoxic drugs and identifying novel mechanisms of CSC maintenance will enable the development of better therapeutic strategies for high-grade serous ovarian cancer.

Significance: We show that chemotherapy enhances proinflammatory macrophage phenotypes that correlate with ovarian cancer progression. Given that macrophages are the most prominent immune cell within these tumors, this work provides the foundation for future translational studies targeting specific macrophage populations during chemotherapy, a promising approach to prevent relapse in ovarian cancer.
Dimensiones política y pública de la orfandad por feminicidio: una revisión de literatura
Authors: Scaramussa da Silva Roberta , Patiño-Orozco Rafael Andrés
Published: September 2024

(analytical)One of the most extreme types of violence against women is femicide, a crime that also affects their surviving children. This paper presents the results of a comprehensive literature review that analyzed how the political and public dimensions of being orphaned due to femicide are presented in academic studies. A total of 22 articles from different countries were identified published between 1958 and 2022 and a Thematic-Categorical Analysis was applied. The results evidenced a clear a-critical and a-historical discourse on this subject. In addition to the absence of official data on this problem, public policies were identified as either inefficient or non-existent. In order to protect this population, the existence of children and adolescents who have been orphaned due to femicide need to be recognized as a social problem and targeted by systematic and efficient actions.
Keywords: Femicide; orphaned children; public policy; literature review.
Pedagogía del cuírlombo: violencia a un padre cuír en la educación infantil
Authors: Padilha Ana Paula Freitas , Vicenzi Vinícius Bertoncini , Farias Dresch Jaime
Published: September 2024

This article presents an everyday experience in the field of early childhood education, specifically colonial cisgender-endosex violence contained in teachers' discourse. Possible forms of resistance based on Queer studies and experiences are presented. The article discusses the colonial cisgenderendosex apparatus through a perspective of biopower, which circulates in the school space in an exclusionary, pejorative and discriminatory way. The study draws on decolonial and post-structuralist theory, articulated with emerging issues from queer, feminist and anti-racist production. The results of the research evidence the existence of some escape lines for the school's agency in relation to its cisheteronormative discourse. The discussion focuses on how the intersection of other discourses present in the school, driven by an increased cultural and political visibility of the Queer population, contribute to the construction of Queer Pedagogy.
The identity of Dalechampia subintegra (Euphorbiaceae): synonyms and geographic distribution
Authors: BRIGATO LUIZA OLIVEIRA , PEREIRA-SILVA RAFAELA ALVES , MENDES JONE CLEBSON RIBEIRO , CARNEIRO-TORRES DANIELA SANTOS , MELO ANDRÉ LAURÊNIO DE , CORDEIRO INÊS , SILVA OTÁVIO LUIS MARQUES DA
Published: September 2024

N/A
Rediscovery, amplified description, and taxonomic re-evaluation of Phanera erythropoda var. guangxiensis (Leguminosae, Cercidoideae)
Authors: PENG XIA , JIANG KAI-WEN , XIE ZHI , GU SHI-RAN , WANG XIANG-PING , LI SHI-JIN , SHI MIAO-MIAO , TU TIE-YAO , ZHANG DIAN-XIANG
Published: September 2024

For nearly seven decades, the legume variety Phanera erythropoda var. guangxiensis (D. X. Zhang & T. C. Chen) Mackinder & R. Clark has been known solely from its type gathering, which lacked flowers and possessed only immature fruits. We report the rediscovery of this elusive variety at its type locality in Guangxi, China, including specimens bearing mature flowers. The floral characters observed diverge significantly from those of P. erythropoda, yet exhibit clear affinities with the Lasiobema group within the genus Phanera. With these new data, we provide a comprehensive description of the variety and propose elevating its taxonomic status to that of a distinct species, namely Phanera guangxiensis. We also present an updated key to all Chinese members of the Lasiobema group.
Correction of collection number errors in the protologues of twenty-three names of Chinese vascular plants
Authors: LIN YUN , SUN QIAN , BI HAI-YAN , CHEN TIAN-XIANG
Published: September 2024

Examination and collation of Chinese type specimens from the University Herbarium, University of California, the Harvard University Herbaria and the William and Lynda Steere Herbarium of New York Botanical Garden led to the discovery of errors in the designation of type specimens in the protologues of several names. Following Article 9.2 of the International Code of Nomenclature for algae, fungi, and plants (Shenzhen Code, 2018), typographical errors in the citation of collection numbers in the protologues of 23 Chinese vascular plants were corrected.
One must imagine Sisyphus happy: Integrative taxonomic characterization of 22 new Ceroptres species (Hymenoptera: Cynipidae: Ceroptresini)
Authors: NASTASI LOUIS F. , SMITH CECIL N. , DAVIS CHARLES K. , WARD ANNA K.G. , BROWN GUERIN , ZHANG Y. MILES , ROLLINS SHANNON , FRIESEN CHRIS , TRIBULL CARLY M. , FORBES ANDREW A. , DEANS ANDREW R.
Published: September 2024

We describe new species in the genus Ceroptres Hartig, 1840 (Hymenoptera: Cynipidae: Ceroptresini) represented by voucher material sequenced by Ward et al. (2024). We describe 22 new species, all authored by Nastasi, Smith, & Davis: C. anansii sp. nov., C. anzui sp. nov., C. bruti sp. nov., C. curupira sp. nov., C. daleki sp. nov., C. dandoi sp. nov., C. demerzelae sp. nov., C. iktomii sp. nov., C. jabbai sp. nov., C. jarethi sp. nov., C. lokii sp. nov., C. lupini sp. nov., C. mallowi sp. nov., C. promethei sp. nov., C. sandiegoae sp. nov., C. selinae sp. nov., C. soloi sp. nov., C. songae sp. nov., C. swiperi sp. nov., C. thrymi sp. nov., C. tikoloshei sp. nov., and C. zorroi sp. nov. After our taxonomic treatment, the genus Ceroptres includes 43 species, all but three of which are known from North America. Among our new species are two reared from cecidomyiid midge galls, an association previously recorded but without valid taxonomic association. We provide new records for two additional previously described species; we record C. ensiger (Walsh, 1864) from Pennsylvania and confirm characters for the male, and we record C. lanigerae Ashmead, 1885 from Texas. We also examined several putative species corresponding to either C. cornigera Melika & Buss, 2002 and/or C. frondosae Ashmead, 1896, which we regard as a species complex that requires elucidation in future studies. To enable further studies on Ceroptres, we provide an updated key to North American females. Overall, we find that species of Ceroptres are host specialists associated with a single host gall species or several galls that are phylogenetically or ecologically related. We suggest that there are many North American species of Ceroptres, possibly hundreds, still awaiting collection and characterization.
A Comprehensive Evaluation of Mean and Extreme Climate for the Conformal Cubic Atmospheric Model (CCAM)
Authors: Schroeter Benjamin J. E. , Ng Benjamin , Takbash Alicia , Rafter Tony , Thatcher Marcus
Published: September 2024

This study evaluates the performance of the Conformal Cubic Atmospheric Model (CCAM) in dynamically downscaling fifth major global reanalysis produced by European Centre for Medium-Range Weather Forecasts (ECMWF) (ERA5) reanalysis data from 1985 to 2014, following a 5-yr spinup period. It focuses on daily maximum and minimum temperatures and daily precipitation, comparing CCAM to ERA5 and the Australian Gridded Climate Data (AGCD). The CCAM effectively reduces warm biases in daily minimum temperatures but struggles with cold biases in daily maximum temperatures, particularly in northern Australia during the wet season, possibly due to high-level cloud overestimation. Precipitation tends to be overestimated, especially in extreme rainfall events, though offset by an underestimation of low rainfall. The study showcases improvements in the annual minimum of daily minimum temperatures across most of Australia, while identifying challenges in forecasting cooler extreme temperatures. It adds value to annual maximum daily maximum temperatures in southern Australia but less so in the north. The analysis of the 5% annual exceedance probability (AEP5%) yields mixed results influenced by location and potential ocean temperature changes. Some coastal areas exhibit lost value, possibly linked to ocean temperature shifts. Furthermore, CCAM’s representation of maximum annual daily and 5-day rainfall reveals lost value, particularly in eastern Australia due to an overestimate of extreme rainfall. Despite the challenges of comparing a dynamical downscaling model like CCAM to ERA5, this study highlights its benefits in reducing biases, especially in temperature representation. Given the larger biases in phase 6 of Coupled Model Intercomparison Project (CMIP6) global climate models, CCAM appears suitable for dynamic downscaling in climate projections, emphasizing the need for ongoing model enhancements, including addressing biases related to ephemeral water bodies and extreme rainfall.

Significance Statement

This study critically assesses the performance of the Conformal Cubic Atmospheric Model (CCAM) in dynamically downscaling ERA5 reanalysis data from 1985 to 2014, offering valuable insights into climate modeling. Focusing on temperature and precipitation, CCAM proves effective in mitigating warm biases in daily minimum temperatures but encounters challenges with cold biases in daily maximum temperatures, particularly in northern Australia. The analysis reveals the overestimation of precipitation, especially in extreme events, yet identifies improvements in annual minimum daily minimum temperatures across Australia. The study underscores CCAM’s potential in reducing biases compared to CMIP6 global climate models, making it a promising tool for dynamic downscaling in climate projections. It emphasizes the necessity for ongoing model enhancements, particularly addressing biases related to ephemeral water bodies and extreme rainfall.
“It’s a Battle You Can’t Win”: Domination and Class Differences in Real-World Trust among Black Families
Authors: Tyson Karolyn
Published: September 2024

How does class affect one’s propensity to trust? Previous research finds higher-status actors express less trust than lower-status actors in interpersonal and institutional contexts. Scholars explain this finding as an outcome of structural dependence—when people have few alternative means for accessing valuable resources. In contrast, I find dependence inadequate to explain the relationship I observe between class and institutional trust among black families whose children were recommended for special education and other remedial program placement in an affluent, predominantly white school district. Drawing on retrospective interviews from a community ethnography, findings show that real-world trust decision processes also involve domination. Empirical studies of trust have overlooked the ways trustees—those being given trust—exercise power to achieve deference in trust exchanges, and how trustors—those placing trust in others—deploy their power to withstand trustees’ influence. I argue that trust might best be conceptualized as a two-part decision process, because class and other status resources affect trustors’ freedom to choose at two key junctures: (1) in weighing options and costs of trust errors, and (2) in communicating distrust in face-to-face interactions, where the potential for domination is high. Focusing on intersecting systems of power in authentic trust exchanges, this study shows how middle-class black trustors use symbolic resources to “go up against” the institutional power of educational experts and refuse placement, whereas working-class trustors consent to placement.
Measuring the Social Impact of Social Enterprises–Scale Development and Validation
Authors: Quilloy-Custodio Karen , Newman Alexander , Pyman Amanda
Published: September 2024

Social impact measurement has remained a challenge for both social enterprises (SEs) and scholars in the SE field. Despite increased scholarly attention given to SE social impact and its measurement in recent years, scholars continue to call for more research to advance the approaches for measuring social impact in SEs. This study aims to provide a reliable and valid social impact scale for SEs, which can be used as an alternative or a complementary scale to existing quantitative social impact tools. Through a systematic scale development process, it develops a 31-item multidimensional social impact scale based on the triple bottom line sustainability framework and using perception-based or constituency-based feedback. Data analysis confirms the reliability and validity of the scale across two studies involving different SE samples and country contexts. The study also discusses implications for theory and practice and recommendations for future research.
Understanding the Challenges in the Anti-Human Trafficking Movement in Florida
Authors: Wagers Shelly M. , Grosholz Jessica M. , Stone Sandra , Carter Kailey Pate , Franklin Sarah
Published: September 2024

Florida ranks third in the United States for prevalence rates of human trafficking, but there are still clear gaps in the way we address human trafficking in terms of prevention, intervention, and treatment. To better understand the gaps in services for human trafficking survivors from the perspective of the providers who serve them, we conducted in-depth interviews with anti-trafficking stakeholders in Florida. This comprehensive gap analysis helped shed light on the areas needed to effectively assist human trafficking survivors. This article presents literature on the scope of human trafficking and victim service provision, followed by a presentation of the current study, its methodology and results, and concludes with a discussion of the general implications of these findings as well as practical applications of the results of this study.
Transactional pathways: Institutional possibilities for status and wealth under racial/caste capitalism
Authors: Kornberg Dana
Published: September 2024

I introduce the concept of transactional pathways, coined by anthropologist Jane Guyer, to trace the institutional processes that contribute to uneven and unjust patterns of wealth and status distribution under systems of colonialism and racial/caste capitalism. Transactional pathways employ historical perspectives to reveal how divergent economic institutions and sources of valuation relate to social hierarchies. This approach links everyday economic transactions with patterns of wealth accumulation that are based not only on class, but intersectional social groups including race, caste, and/or ethnicity. Transactional pathways account for the fact that not only do different groups receive different amounts of valuable resources because of uneven distribution, but they have variable access to the symbolic power required to define which resources are deemed valuable in the first place and to monopolize them accordingly. The article briefly surveys foundational concepts from the economic anthropology literature before detailing transactional pathways. It introduces the case of attempted formalization of waste collection and recycling in Delhi, India, using the related concepts of thresholds and conversions to analyze key moments when wealth and status accumulation becomes especially possible in institutionally plural contexts.
Ecological Dominance Orientation as a predictor of Wildlife Value Orientations and Support for Lethal Wildlife Management
Authors: Smith Kyle , Boehne Shane , Boley Bynum B. , D’Angelo Gino J.
Published: September 2024

While many environmental psychologists have relied on the Wildlife Value Orientations (WVOs) scale to understand the individual patterns in cognitions and behaviors related to wildlife, limits in scope constrain its application across other topics. Conversely, Ecological Dominance Orientation (EDO), defined as preference to maintain an anthropocentric arrangement between humans and the natural environment, has demonstrated applicability across a variety of contexts. Despite both constructs being applied in the field, the relationship between the two constructs remains understudied. We sought to understand the associations between EDO and WVO within the context of support for lethal control of deer within two communities located in Georgia, USA. Results suggest that EDO strongly predicted WVOs and had a strong, positive direct and indirect effect on support for lethal control. Future research centered on EDO may help bridge our understanding of individuals’ beliefs about wildlife and other parts of the natural world.
Research on pure azimuth passive positioning of unmanned aerial vehicle formation in electromagnetic silence environment
Authors: Qian Cheng
Published: September 2024

In the electromagnetic silence environment, for the azimuth-only passive localization problem in the conical formation, it was concluded that there was a deviation between the ideal standard formation and the actual formation. These disturbance deviations should be eliminated to make the UAV reach the ideal formation state. Therefore, the adjustment model of individual UAV, the directed graph model of formation node and the MDP model of adjustment strategy are constructed. Based on the relevant factor model constructed, the azimuth-only passive localization model in conical formation is established and solved in MATLAB. Finally, experiments and analysis are carried out in the simulation environment, and the effectiveness and feasibility of the proposed algorithm are proved.
Multiphase time-varying batch process monitoring based on stage moving model migration
Authors: Zhao Luping , Chen Zhongren
Published: September 2024

To improve product qualities and obtain maximum comprehensive economic benefits from batch process production, it is of great practical significance to optimize the operation of batch production processes. Considering the multiphase and slow time-varying characteristics, a multiphase time-varying batch process monitoring method is proposed based on stage moving model migration technology. Firstly, the sliding windows are constructed with moving phases, where the moving of different phases is decided by the influence of the process variables to the final product. And time slices are the basic units for building the regression models. Secondly, to analyze and capture the relationship between the process variables of both the old mode and new mode and the final quality variable, the JY-PLS algorithm is utilized on each time slice within sliding windows for quality prediction. Then, monitoring indexes and corresponding control limits are calculated and used for process monitoring. The application to a real multiphase time-varying batch process, the start-up process of injection molding process, proved the effectiveness of the proposed method.
“AI Can’t Steal My Soul”: In the Age of AI, the Human Touch is Paramount for the Craft of Managing Change
Authors: Gonzalez Katerina , Kanitz Rouven , Briker Roman
Published: September 2024

Artificial intelligence (AI) models are increasingly adopted as tools to enhance change management processes. Although many change managers are excited about AI's potential, others worry that their contributions may become obsolete. We explore the tension between job augmentation and automation and how it affects change management professionals. We argue that change managers need to approach their profession as a context-sensitive craft. We highlight elements that are likely to become increasingly central for change managers’ success: (a) high-level skills—relational mastery and systems thinking—and (b) the continued development of specific attitudes—authentic dedication and communal co-presence. In contrast, other tasks that change managers were previously engaged with (e.g., routine communication, reporting) will play a smaller role in the future. We advocate for approaching change work as an AI-augmented craft and call for a critical reflection of the skills and attitudes necessary to effectively diagnose, envision, and mobilize change in the age of AI.
Tracks of change: The rise and fall of Bolivia's National Railway Company (ENFE): 1965–1995
Authors: Contreras Manuel E.
Published: September 2024

This article examines the Bolivian State Railway Company (ENFE) from its inception in 1965 to its privatisation in 1995, focusing on its structural evolution, growth, and modernisation in the context of Bolivian state capitalism. It underscores ENFE's substantial contribution to Bolivia's economy, particularly in freight and passenger transport. By comparing ENFE’s labour productivity and financial ratios with other Latin American state railways, this study reveals ENFE's distinct capability for revenue generation due to limited road competition. Key primary sources include ENFE annual reports, World Bank loan documents, archival correspondence, transport studies, and the local press. This article argues that ENFE successfully addressed transportation challenges and contributed to Bolivian economic development. These findings provide valuable insights into Bolivian economic history and Latin American railway historiography through a case study of a strategic state-owned enterprise, illustrating the potential of leveraging World Bank sources for future comparative research on Latin American railways.
The Psychedelic Renaissance: A Catholic Perspective
Authors: Carroll Thomas
Published: September 2024

After being outlawed in 1970, psychedelics have reemerged in the consciousness of Western society in the form of the so-called psychedelic renaissance. This has led to widespread interest in psychedelic compounds being used for recreation, treatment of mental illness and addiction, and even the so-called “enhancement” of individuals and society. This renewed interest in psychedelics has resulted in seemingly endless publications in both the popular and the academic press, including authors from fields as diverse as philosophy, theology, pharmacology, neuroscience, and clinical medicine. A common thread in this developing literature is the claim that psychedelic compounds mediate their reported benefits by inducing the so-called psychedelic mystical experience (PME). The nature of PME is hotly debated, with some claiming that it is entirely psychological and others proposing that it involves contact with extramental reality. This raises a number of important questions for Catholics, especially whether PME should be considered properly “mystical,” how PME compares with traditionally understood Catholic mysticism, and whether, and if so under what conditions, psychedelics could be licitly used by the Catholic faithful. This paper is an attempt to begin the process of reconciling empiric scientific data regarding psychedelics generally, and PME specifically, with Catholic philosophical and theological considerations, with the goal of both providing recommendations regarding the licitness of the use of psychedelic compounds and inviting conversation about this important and challenging topic.

Over the past 20 years, there has been a renewed interest in of psychedelics. Many articles have been published extoling the benefits of psychedelics, including for the treatment of mental illness and addiction, recreation, and “enhancement” of individuals and society. A common claim is that the benefits of psychedelics are a result of the psychedelic mystical experience (PME). This paper considers both the use of psychedelics and PME from the perspective of Catholic theology, provides recommendations about their use for the Catholic faithful, and invites further conversation about this important and challenging topic.

Short Summary

This paper considers challenges posed by psychedelics, considers licitness of use, and calls for further discussion.