bluuebunny/crossref_metadata_2025 huggingface dataset:
Offering a Demand‐Based Charging Method Using the GBO Algorithm and Fuzzy Logic in the WRSN for Wireless Power Transfer by UAV
Authors: Habibi Payman , Hassanifard Goran , Ghaderzadeh Abdulbaghi , Nosratpour Arez
Published: May 2023

An extremely high number of geographically dispersed, energy‐limited sensor nodes make up wireless sensor networks. One of the critical difficulties with these networks is their network lifetime. Wirelessly charging the sensors continuously is one technique to lengthen the network’s lifespan. In order to compensate for the sensor nodes’ energy through a wireless medium, a mobile charger (MC) is employed in wireless sensor networks (WRSN). Designing a charging scheme that best extends the network’s lifetime in such a situation is difficult. In this paper, a demand‐based charging method using unmanned aerial vehicles (UAVs) is provided for wireless rechargeable sensor networks. In this regard, first, sensors are grouped according to their geographic position using the K‐means clustering technique. Then, with the aid of a fuzzy logic system, these clusters are ranked in order of priority based on the parameters of the average percentage of battery life left in the sensor nodes’ batteries, the number of sensors, and critical sensors that must be charged, and the distance between each cluster’s center and the MC charging station. It then displays the positions of the UAV to choose the crucial sensor nodes using a routing algorithm based on the shortest and most vital path in each cluster. Notably, the gradient‐based optimization (GBO) algorithm has been applied in this work for intracluster routing. A case study for a wireless rechargeable sensor network has been carried out in MATLAB to assess the performance of the suggested design. The outcomes of the simulation show that the suggested technique was successful in extending the network’s lifetime. Based on the simulation results, compared to the genetic algorithm, the proposed algorithm has been able to reduce total energy consumption, total distance during the tour, and total travel delay by 26%, 17.2%, and 25.4%, respectively.
Comprehensive Analysis of the Expression, Prognostic Value, and Immune Infiltration Activities of GABRD in Colon Adenocarcinoma
Authors: Huang Fakun , Wang Zhengyang , Zhu Liyue , Lin Changqing , Wang Jia-xing
Published: May 2023

Colon adenocarcinoma (COAD) is one of the tumors with the highest mortality rates. It is of the utmost significance to make an accurate prognostic assessment and to tailor one’s treatment to the specific needs of the patient. Multiple lines of evidence point to the possibility that genetic variables and clinicopathological traits are connected to the onset and development of cancer. In the past, a number of studies have revealed that gamma-aminobutyric acid type A receptor subunit delta (GABRD) plays a role in the advancement of a number of different cancers. However, its function in COAD was rarely reported. In this study, we analyzed TCGA datasets and identified 29 survival-related differentially expressed genes (DEGs) in COAD patients. In particular, GABRD expression was noticeably elevated in COAD specimens. There was a correlation between high GABRD expression and an advanced clinical stage. According to the results of the survival tests, patients whose GABRD expression was high had a lower overall survival time and progression-free survival time than those whose GABRD expression was low. GABRD expression was found to be an independent predictive predictor for overall survival, as determined by multivariate COX regression analysis. Additionally, the predictive nomogram model can accurately predict the fate of individuals with COAD. In addition, we observed that GABRD expressions were positively associated with the expression of T cells regulatory (Tregs), macrophages M0, while negatively associated with the expression of T cells CD8, T cells follicular helper, macrophages M1, dendritic cells activated, eosinophils, and T cells CD4 memory activated. The IC50 of BI-2536, bleomycin, embelin, FR-180204, GW843682X, LY317615, NSC-207895, rTRAIL, and VX-11e was higher in the GABRD high-expression group. In conclusion, we have shown evidence that GABRD is a novel biomarker that is connected with immune cell infiltration in COAD and may be utilized to predict the prognosis of COAD patients.
On Annihilated Points and Approximate Fixed Points of General Higher-Order Nonexpansive Mappings
Authors: Gordon Joseph Frank , Shaikh Abdul Hayee , Annan Augustine , Arthur Yarhands Dissou , Akweittey Emmanuel , Obeng Benjamin Adu
Published: May 2023

In this paper, we extend the results obtained by Ezearn on annihilated points for his higher-order nonexpansive mappings to the context of general higher-order nonexpansive mappings. Precisely in his thesis, Ezearn introduced the concept of annihilated points, which extends the notion of fixed points, and it is only meaningful in the context of higher-order nonexpansive mappings and gave some mild conditions when the annihilated points could exist in strictly convex Banach spaces. In the last direction, we also extend Ezearn’s result on the approximate fixed point sequence for higher-order nonexpansive mappings to general higher-order nonexpansive mappings.
Supplementary file 3: Supplementary Tables. from circFNDC3B Accelerates Vasculature Formation and Metastasis in Oral Squamous Cell Carcinoma
Authors: Li Xiang , Wang Chenxing , Zhang Hang , Li Yangjie , Hou Deqiang , Liu Dingshan , Xu Rongyao , Cheng Jie , Liu Laikui , Fu Yu , Ye Jinhai , Jiang Hongbing
Published: May 2023

Supplementary Tables.
Table S1 from Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma
Authors: Zhang Hanyun , AbdulJabbar Khalid , Moore David A. , Akarca Ayse , Enfield Katey S.S. , Jamal-Hanjani Mariam , Raza Shan E. Ahmed , Veeriah Selvaraju , Salgado Roberto , McGranahan Nicholas , Le Quesne John , Swanton Charles , Marafioti Teresa , Yuan Yinyin
Published: May 2023

Differentially expressed genes in TCGA LUSC and LUAD patients with high versus low S_intra/immune
Supplementary Figures from The Macrophage-Associated LncRNA MALR Facilitates ILF3 Liquid–Liquid Phase Separation to Promote HIF1α Signaling in Esophageal Cancer
Authors: Liu Jia , Liu Ze-Xian , Li Jia-Jun , Zeng Zhao-Lei , Wang Jin-Hong , Luo Xiao-Jing , Wong Chau-Wei , Zheng Jia-Bo , Pu Heng-Ying , Mo Hai-Yu , Sheng Hui , Wu Qi-Nian , Li Hao , Wan Gang , Li Bo , Wang De-shen , Xu Rui-Hua , Ju Huai-Qiang
Published: May 2023

Supplementary Figures
Data from Spatial transcriptomics depict ligand-receptor crosstalk heterogeneity at the tumor-stroma interface in long-term ovarian cancer survivors
Authors: Ferri-Borgogno Sammy , Zhu Ying , Sheng Jianting , Burks Jared K. , Gomez Javier A. , Wong Kwong Kwok , Wong Stephen T. C. , Mok Samuel C.
Published: May 2023

Abstract
Advanced high-grade serous ovarian cancer (HGSC) is an aggressive disease that accounts for 70% of all ovarian cancer deaths. Nevertheless, 15% of patients diagnosed with advanced HGSC survive more than 10 years. The elucidation of predictive markers of these long-term survivors (LTS) could help identify therapeutic targets for the disease, and thus improve patient survival rates. To investigate the stromal heterogeneity of the tumor microenvironment (TME) in ovarian cancer, we used spatial transcriptomics to generate spatially resolved transcript profiles in treatment naïve advanced HGSC from LTS and short-term survivors (STS) and determined the association between cancer-associated fibroblasts (CAF) heterogeneity and survival in patients with advanced HGSC. Spatial transcriptomics and single-cell RNA sequencing data were integrated to distinguish tumor and stroma regions, and a computational method was developed to investigate spatially resolved ligand-receptor interactions between various tumor and CAF subtypes in the TME. A specific subtype of CAFs and its spatial location relative to a particular ovarian cancer cell subtype in the TME correlated with long-term survival in advanced HGSC patients. Also, increased APOE-LRP5 crosstalk occurred at the stroma-tumor interface in tumor tissues from STS compared to LTS. These findings were validated using multiplex immunohistochemistry. Overall, this spatial transcriptomics analysis revealed spatially resolved CAF-tumor crosstalk signaling networks in the ovarian TME that are associated with long-term survival of HGSC patients. Further studies to confirm whether such crosstalk plays a role in modulating the malignant phenotype of HGSC and could serve as a predictive biomarker of patient survival are warranted.
Data from Spatial Transcriptomics Depict Ligand–Receptor Cross-talk Heterogeneity at the Tumor-Stroma Interface in Long-Term Ovarian Cancer Survivors
Authors: Ferri-Borgogno Sammy , Zhu Ying , Sheng Jianting , Burks Jared K. , Gomez Javier A. , Wong Kwong Kwok , Wong Stephen T.C. , Mok Samuel C.
Published: May 2023

Abstract
Advanced high-grade serous ovarian cancer (HGSC) is an aggressive disease that accounts for 70% of all ovarian cancer deaths. Nevertheless, 15% of patients diagnosed with advanced HGSC survive more than 10 years. The elucidation of predictive markers of these long-term survivors (LTS) could help identify therapeutic targets for the disease, and thus improve patient survival rates. To investigate the stromal heterogeneity of the tumor microenvironment (TME) in ovarian cancer, we used spatial transcriptomics to generate spatially resolved transcript profiles in treatment-naïve advanced HGSC from LTS and short-term survivors (STS) and determined the association between cancer-associated fibroblasts (CAF) heterogeneity and survival in patients with advanced HGSC. Spatial transcriptomics and single-cell RNA-sequencing data were integrated to distinguish tumor and stroma regions, and a computational method was developed to investigate spatially resolved ligand–receptor interactions between various tumor and CAF subtypes in the TME. A specific subtype of CAFs and its spatial location relative to a particular ovarian cancer cell subtype in the TME correlated with long-term survival in patients with advanced HGSC. Also, increased APOE-LRP5 cross-talk occurred at the stroma-tumor interface in tumor tissues from STS compared with LTS. These findings were validated using multiplex IHC. Overall, this spatial transcriptomics analysis revealed spatially resolved CAF-tumor cross-talk signaling networks in the ovarian TME that are associated with long-term survival of patients with HGSC. Further studies to confirm whether such cross-talk plays a role in modulating the malignant phenotype of HGSC and could serve as a predictive biomarker of patient survival are warranted.
Significance:
Generation of spatially resolved gene expression patterns in tumors from patients with ovarian cancer surviving more than 10 years allows the identification of novel predictive biomarkers and therapeutic targets for better patient management.

See related commentary by Kelliher and Lengyel, p. 1383
Data from Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma
Authors: Zhang Hanyun , AbdulJabbar Khalid , Moore David A. , Akarca Ayse , Enfield Katey S.S. , Jamal-Hanjani Mariam , Raza Shan E. Ahmed , Veeriah Selvaraju , Salgado Roberto , McGranahan Nicholas , Le Quesne John , Swanton Charles , Marafioti Teresa , Yuan Yinyin
Published: May 2023

Abstract
Beyond tertiary lymphoid structures, a significant number of immune-rich areas without germinal center-like structures are observed in non–small cell lung cancer. Here, we integrated transcriptomic data and digital pathology images to study the prognostic implications, spatial locations, and constitution of immune rich areas (immune hotspots) in a cohort of 935 patients with lung cancer from The Cancer Genome Atlas. A high intratumoral immune hotspot score, which measures the proportion of immune hotspots interfacing with tumor islands, was correlated with poor overall survival in lung squamous cell carcinoma but not in lung adenocarcinoma. Lung squamous cell carcinomas with high intratumoral immune hotspot scores were characterized by consistent upregulation of B-cell signatures. Spatial statistical analyses conducted on serial multiplex IHC slides further revealed that only 4.87% of peritumoral immune hotspots and 0.26% of intratumoral immune hotspots were tertiary lymphoid structures. Significantly lower densities of CD20+CXCR5+ and CD79b+ B cells and less diverse immune cell interactions were found in intratumoral immune hotspots compared with peritumoral immune hotspots. Furthermore, there was a negative correlation between the percentages of CD8+ T cells and T regulatory cells in intratumoral but not in peritumoral immune hotspots, with tertiary lymphoid structures excluded. These findings suggest that the intratumoral immune hotspots reflect an immunosuppressive niche compared with peritumoral immune hotspots, independent of the distribution of tertiary lymphoid structures. A balance toward increased intratumoral immune hotspots is indicative of a compromised antitumor immune response and poor outcome in lung squamous cell carcinoma.
Significance:
Intratumoral immune hotspots beyond tertiary lymphoid structures reflect an immunosuppressive microenvironment, different from peritumoral immune hotspots, warranting further study in the context of immunotherapies.
Data from Polyunsaturated fatty acid-bound alpha-fetoprotein promotes immune suppression by altering human dendritic cell metabolism
Authors: Munson Paul V. , Adamik Juraj , Hartmann Felix J. , Favaro Patricia M. B. , Ho Daniel , Bendall Sean C. , Combes Alexis J. , Krummel Matthew F. , Zhang Karen , Kelley Robin K. , Butterfield Lisa H.
Published: May 2023

Abstract
Alpha-fetoprotein (AFP) is expressed by stem-like and poor outcome hepatocellular cancer tumors and is a clinical tumor biomarker. AFP has been demonstrated to inhibit dendritic cell differentiation and maturation and to block oxidative phosphorylation. To identify the critical metabolic pathways leading to human dendritic cell functional suppression, here we utilized two recently described single cell profiling methods, scMEP (single-cell metabolic profiling) and SCENITH (single-cell energetic metabolism by profiling translation inhibition). Glycolytic capacity and glucose dependence of dendritic cells was significantly increased by tumor-derived, but not normal cord blood-derived, AFP, leading to increased glucose uptake and lactate secretion. Key molecules in the electron transport chain in particular were regulated by tumor-derived AFP. These metabolic changes occurred at mRNA and protein levels, with negative impact on dendritic cell stimulatory capacity. Tumor-derived AFP bound significantly more polyunsaturated fatty acids than cord blood-derived AFP. Polyunsaturated fatty acids bound to AFP increased metabolic skewing and promoted dendritic cell functional suppression. Polyunsaturated fatty acids inhibited dendritic cell differentiation in vitro, and ω-6 polyunsaturated fatty acids conferred potent immunoregulation when bound to tumor-derived AFP. Together, these findings provide mechanistic insights into how AFP antagonizes the innate immune response to limit anti-tumor immunity.
Data from Computational and Functional Analyses of HER2 Mutations Reveal Allosteric Activation Mechanisms and Altered Pharmacologic Effects
Authors: Ishiyama Noboru , O'Connor Matthew , Salomatov Andrei , Romashko Darlene , Thakur Shalabh , Mentes Ahmet , Hopkins Julia F. , Frampton Garrett M. , Albacker Lee A. , Kohlmann Anna , Roberts Christopher , Buck Elizabeth
Published: May 2023

Abstract
Amplification of HER2 can drive the proliferation of cancer cells, and several inhibitors of HER2 have been successfully developed. Recent advances in next-generation sequencing now reveal that HER2 is subject to mutation, with over 2,000 unique variants observed in human cancers. Several examples of oncogenic HER2 mutations have been described, and these primarily occur at allosteric sites outside the ATP-binding site. To identify the full spectrum of oncogenic HER2 driver mutations aside from a few well-studied mutations, we developed mutation-allostery-pharmacology (MAP), an in silico prediction algorithm based on machine learning. By applying this computational approach to 820 single-nucleotide variants, a list of 222 known and potential driver mutations was produced. Of these 222 mutations, 111 were screened by Ba/F3-retrovirus proliferation assays; 37 HER2 mutations were experimentally determined to be driver mutations, comprising 15 previously characterized and 22 newly identified oncogenic mutations. These oncogenic mutations mostly affected allosteric sites in the extracellular domain (ECD), transmembrane domain, and kinase domain of HER2, with only a single mutation in the HER2 orthosteric ATP site. Covalent homodimerization was established as a common mechanism of activation among HER2 ECD allosteric mutations, including the most prevalent HER2 mutation, S310F. Furthermore, HER2 allosteric mutants with enhanced covalent homodimerization were characterized by altered pharmacology that reduces the activity of existing anti-HER2 agents, including the mAb trastuzumab and the tyrosine kinase inhibitor lapatinib. Overall, the MAP-scoring and functional validation analyses provided new insights into the oncogenic activity and therapeutic targeting of HER2 mutations in cancer.
Significance:
This study identified new oncogenic HER2 allosteric mutations, including ECD mutations that share covalent dimerization as a mechanism of oncogenicity, suggesting the need for novel inhibitors to treat HER2-mutant cancers.
Data from Ablation of p57+ Quiescent Cancer Stem Cells Suppresses Recurrence After Chemotherapy of Intestinal Tumors
Authors: Oka Takeru , Higa Tsunaki , Sugahara Osamu , Koga Daisuke , Nakayama Shogo , Nakayama Keiichi I.
Published: May 2023

Abstract
Quiescent cancer stem cells (CSCs) are resistant to conventional anti-cancer treatments and have been shown to contribute to disease relapse after therapy in some cancer types. The identification and characterization of quiescent CSCs could facilitate the development of strategies to target this cell population and block recurrence. Here, we established a syngeneic orthotopic transplantation model in mice based on intestinal cancer organoids to profile quiescent CSCs. Single-cell transcriptomic analysis of the primary tumors formed in vivo revealed that conventional Lgr5high intestinal CSCs comprise both actively and slowly cycling subpopulations, the latter of which specifically expresses the cyclin-dependent kinase inhibitor p57. Tumorigenicity assays and lineage tracing experiments showed that the quiescent p57+ CSCs contribute in only a limited manner to steady-state tumor growth but they are chemotherapy resistant and drive post-therapeutic cancer recurrence. Ablation of p57+ CSCs suppressed intestinal tumor regrowth after chemotherapy. Together, these results shed light on the heterogeneity of intestinal CSCs and reveal p57+ CSCs as a promising therapeutic target for malignant intestinal cancer.
Data from RBM10 Loss Promotes EGFR-Driven Lung Cancer and Confers Sensitivity to Spliceosome Inhibition
Authors: Bao Yufang , Zhang Sirui , Zhang Xiaoyu , Pan Yunjian , Yan Yueren , Wang Ning , Ren Yunpeng , Zuo Ji , Zong Wei-Xing , Wang Zefeng , Wang Yongbo
Published: May 2023

Abstract
In lung adenocarcinoma (LUAD), loss-of-function mutations in the splicing factor RBM10 frequently co-occur with oncogenic EGFR mutations. A detailed understanding of the functional consequences and therapeutic impact of RBM10 loss in EGFR-mutant LUAD could help identify more effective treatment strategies. Here, analysis of LUAD data sets indicated that RBM10 mutations are mutually exclusive with mutations in the tumor suppressor gene TP53. In an EGFR-driven LUAD mouse model, lung-specific ablation of either Rbm10 or Trp53 similarly promoted tumor development, leading to overlapping gene expression changes enriched in cancer-related pathways. RBM10 loss induced key RNA splicing changes concordant in mice and LUAD patients. Importantly, RBM10 deficiency conferred high sensitivity to spliceosome inhibition in EGFR-mutated LUAD cells. Combined treatment with spliceosome inhibitor improved the therapeutic efficacy of EGFR tyrosine kinase inhibitor osimertinib and overcame drug resistance, especially in RBM10-deficient LUAD. Together, this study establishes RBM10 as a tumor suppressor akin to p53 and provides a therapeutic strategy of targeting the splicing machinery in EGFR-driven LUAD.
Significance:
Loss of the splicing factor RBM10 is mutually exclusive with p53 mutations, promotes tumorigenesis, and enhances the efficacy of spliceosome inhibition in EGFR-driven lung cancer.
Data from The macrophage-associated lncRNA MALR facilitates ILF3 liquid-liquid phase separation to promote HIF1α signaling in esophageal cancer
Authors: Liu Jia , Liu Ze-Xian , Li Jia-Jun , Zeng Zhao-Lei , Wang Jin-Hong , Luo Xiao-Jing , Wong Chau-Wei , Zheng Jia-Bo , Pu Heng-Ying , Mo Hai-yu , Sheng Hui , Wu Qi-Nian , Li Hao , Wan Gang , Li Bo , Wang De-shen , Xu Rui-Hua , Ju Huai-Qiang
Published: May 2023

Abstract
Tumor-associated macrophages (TAM) are among the most abundant immune cells in the tumor microenvironment and are important mediators of tumor development and progression. Here, we identified a macrophage-associated long non-coding RNA (lncRNA), MALR, that facilitates progression of esophageal squamous cell carcinoma (ESCC). TAM-mediated secretion of TNFα drove MALR upregulation in ESCC cells. MALR promoted aerobic glycolytic activity and facilitated angiogenesis by activating the HIF1α signaling pathway. Mechanistically, MALR bound the dsRBD1 domain of interleukin enhancer-binding factor 3 (ILF3), promoting ILF3 protein stability and ILF3-mediated liquid-liquid phase separation (LLPS), thereby enhancing HIF1α mRNA stability by preventing PARN-mediated degradation. Loss of MALR suppressed cell line-based and patient-derived xenograft tumor growth. Clinically, high expression of MALR positively correlated with HIF1α target gene expression and indicated poor prognoses for esophageal cancer patients. Overall, this study uncovers the physiological roles of MALR/ILF3-mediated LLPS in tumor microenvironment remodeling, highlighting the MALR-ILF3-HIF1α axis as a potential target for cancer therapy.
Data from Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors
Authors: Yoon Sang Jun , Combs Joseph A. , Falzone Aimee , Prieto-Farigua Nicolas , Caldwell Samantha , Ackerman Hayley D. , Flores Elsa R. , DeNicola Gina M.
Published: May 2023

Abstract
Cysteine plays critical roles in cellular biosynthesis, enzyme catalysis, and redox metabolism. The intracellular cysteine pool can be sustained by cystine uptake or de novo synthesis from serine and homocysteine. Demand for cysteine is increased during tumorigenesis for generating glutathione to deal with oxidative stress. While cultured cells have been shown to be highly dependent on exogenous cystine for proliferation and survival, how diverse tissues obtain and use cysteine in vivo has not been characterized. We comprehensively interrogated cysteine metabolism in normal murine tissues and cancers that arise from them using stable isotope 13C1-serine and 13C6-cystine tracing. De novo cysteine synthesis was highest in normal liver and pancreas and absent in lung tissue, while cysteine synthesis was either inactive or downregulated during tumorigenesis. By contrast, cystine uptake and metabolism to downstream metabolites was a universal feature of normal tissues and tumors. However, differences in glutathione labeling from cysteine were evident across tumor types. Thus, cystine is a major contributor to the cysteine pool in tumors, and glutathione metabolism is differentially active across tumor types.
Data from Enhancer Coamplification and Hijacking Promote Oncogene Expression in Liposarcoma
Authors: Liu Tingting , Wang Juan , Yang Hongbo , Jin Qiushi , Wang Xiaotao , Fu Yihao , Luan Yu , Wang Qixuan , Youngblood Mark W. , Lu Xinyan , Casadei Lucia , Pollock Raphael , Yue Feng
Published: May 2023

Abstract
Liposarcoma (LPS) is the most common soft-tissue sarcoma in adults with two major subtypes, well differentiated and dedifferentiated. Both subtypes are characterized with the pathognomonic giant ring or marker chromosomes that harbor high copy numbers of known oncogenes. Here, we reported a comprehensive molecular characterization of both tumor and normal tissues from the same patients with LPS, including whole-genome sequencing (WGS), transcriptome, enhancer landscape, and genome-wide three-dimensional (3D) genome structure by Hi-C. Tumor-specific transcripts and regulatory elements were identified, and enhancer coamplification and hijacking events were discovered as novel mechanisms upregulating oncogenes such as MDM2, CDK4, and HMGA2. Combining Hi-C, optical mapping, nanopore long reads, and WGS data partially resolved complex structural variations and reconstructed the local genome and the giant chromosome. Overall, this study provides a comprehensive resource for LPS research and offers insights into how altered enhancers and the 3D genome contribute to gene dysregulation in cancer.
Significance:
Comprehensive profiling of the enhancer landscape and 3D genome structure in liposarcoma identifies extensive enhancer-oncogene coamplification and enhancer hijacking events, deepening the understanding of how oncogenes are regulated in cancer.
Supplementary Table S2: Frequency of tissue-agnostic targets in other additional different tumors (alphabetically arranged) in AACR GENIE v.13 from Tumor-Agnostic Precision Medicine from the AACR GENIE Database: Clinical Implications
Authors: Gouda Mohamed A. , Nelson Blessie E. , Buschhorn Lars , Wahida Adam , Subbiah Vivek
Published: May 2023

Frequency of tissue-agnostic targets in other additional different tumors (alphabetically arranged) in AACR GENIE v.13
Supplementary Figure S4 from DNA-Methylome–Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy
Authors: Tawk Bouchra , Rein Katrin , Schwager Christian , Knoll Maximilian , Wirkner Ute , Hörner-Rieber Juliane , Liermann Jakob , Kurth Ina , Balermpas Panagiotis , Rödel Claus , Linge Annett , Löck Steffen , Lohaus Fabian , Tinhofer Ingeborg , Krause Mechtild , Stuschke Martin , Grosu Anca Ligia , Zips Daniel , Combs Stephanie E. , Belka Claus , Stenzinger Albrecht , Herold-Mende Christel , Baumann Michael , Schirmacher Peter , Debus Jürgen , Abdollahi Amir
Published: May 2023

Supplementary Figure 4 (Top). CD8 T cell enrichment is prognostic for Overall Survival (OS), local recurrence (LR) and disease progression but not for distant metastasis (DM) in HPV negative HNSCC in the DKTK-ROG cohort (n=88). (Bottom) After adjusting for Immune cell Infiltration, Hypoxia-M remained an independent prognosticator for local recurrence (HR=3.06, p<0.01) and for disease progression (HR=2.14, p<0.04) with a trend towards worsened OS (HR=1.92, p<0.09). CD8-IHC staining was an independent prognosticator for local recurrence (HR=0.41, p<0.03) an
Supplementary Table S1 from p38MAPKα Stromal Reprogramming Sensitizes Metastatic Breast Cancer to Immunotherapy
Authors: Faget Douglas V. , Luo Xianmin , Inkman Matthew J. , Ren Qihao , Su Xinming , Ding Kai , Waters Michael R. , Raut Ganesh Kumar , Pandey Gaurav , Dodhiawala Paarth B. , Ramalho-Oliveira Renata , Ye Jiayu , Cole Thomas , Murali Bhavna , Zheleznyak Alexander , Shokeen Monica , Weiss Kurt R. , Monahan Joseph B. , DeSelm Carl J. , Lee Adrian V. , Oesterreich Steffi , Weilbaecher Katherine N. , Zhang Jin , DeNardo David G. , Stewart Sheila A.
Published: May 2023

Table containing all of our reagents
Data from p38MAPKα Stromal Reprogramming Sensitizes Metastatic Breast Cancer to Immunotherapy
Authors: Faget Douglas V. , Luo Xianmin , Inkman Matthew J. , Ren Qihao , Su Xinming , Ding Kai , Waters Michael R. , Raut Ganesh Kumar , Pandey Gaurav , Dodhiawala Paarth B. , Ramalho-Oliveira Renata , Ye Jiayu , Cole Thomas , Murali Bhavna , Zheleznyak Alexander , Shokeen Monica , Weiss Kurt R. , Monahan Joseph B. , DeSelm Carl J. , Lee Adrian V. , Oesterreich Steffi , Weilbaecher Katherine N. , Zhang Jin , DeNardo David G. , Stewart Sheila A.
Published: May 2023

Abstract
Metastatic breast cancer is an intractable disease that responds poorly to immunotherapy. We show that p38MAPKα inhibition (p38i) limits tumor growth by reprogramming the metastatic tumor microenvironment in a CD4+ T cell-, IFNγ-, and macrophage-dependent manner. To identify targets that further increased p38i efficacy, we utilized a stromal labeling approach and single-cell RNA sequencing. Thus, we combined p38i and an OX40 agonist that synergistically reduced metastatic growth and increased overall survival. Intriguingly, patients with a p38i metastatic stromal signature had better overall survival that was further improved by the presence of an increased mutational load, leading us to ask if our approach would be effective in antigenic breast cancer. The combination of p38i, anti-OX40, and cytotoxic T-cell engagement cured mice of metastatic disease and produced long-term immunologic memory. Our findings demonstrate that a detailed understanding of the stromal compartment can be used to design effective antimetastatic therapies.
Significance:
Immunotherapy is rarely effective in breast cancer. We dissected the metastatic tumor stroma, which revealed a novel therapeutic approach that targets the stromal p38MAPK pathway and creates an opportunity to unleash an immunologic response. Our work underscores the importance of understanding the tumor stromal compartment in therapeutic design.
Data from Clonal spreading of tumor-infiltrating T cells underlies the robust antitumor immune responses
Authors: Aoki Hiroyasu , Tsunoda Mikiya , Ogiwara Haru , Shimizu Haruka , Abe Haruka , Ogawa Tatsuro , Abe Takaya , Shichino Shigeyuki , Matsushima Kouji , Ueha Satoshi
Published: May 2023

Abstract
The repertoire of tumor-infiltrating T cells is an emerging method for characterizing effective antitumor T-cell responses. Oligoclonal expansion of the tumor T-cell repertoire has been evaluated; however, their association with antitumor effects is unclear. We demonstrate here that the polyclonal fraction of the tumor-reactive T-cell repertoire, consisting of relatively minor clones, increased in tumor-bearing mice treated with monoclonal anti-PD-L1 or anti-CD4, which correlated with antitumor effects. Meanwhile, the size of the oligoclonal fraction consisting of major clones remained unchanged. Moreover, the polyclonal fraction was enriched in progenitor exhausted T cells, which are essential for a durable antitumor response, and was more dependent on CCR7+ migratory dendritic cells, which are responsible for priming tumor-reactive T cells in the tumor-draining lymph nodes. These results suggest that the expansion of diverse tumor-reactive clones (“clonal spreading”) represents characteristics of antitumor T-cell responses induced by anti-CD4 and anti-PD-L1 treatment.
Supplementary Figure S6 from Interethnic Differences in Bladder Cancer Incidence and the Association between Type 2 Diabetes and Bladder Cancer in the Multiethnic Cohort Study
Authors: Bogumil David , Cortessis Victoria K. , Wilkens Lynne R. , Le Marchand Loïc , Haiman Christopher A. , Maskarinec Gertraud , Setiawan Veronica Wendy
Published: May 2023

Supplementary Figure 6 Association between Any T2D and bladder cancer in the multiethnic sample stratified by sex, smoking status, alcohol consumption, and BMI, with censorship of BCA cases that occurred within 2 years of incident T2D as non-cases. Models adjusted for pack-years smoked (0, 1-10, 11-20, 21-30, 31-40, >40), alcohol consumption (<1 drinks/month, ≤1 drinks/day, >1 drinks/day), sex (male, female), number of cigarettes smoked per day among smokers (5 cigarettes or less, 6-10 cigarettes, 11-20, 21-30, 31 or more), race/ethnicity (European American, African American, Japanese American, Latin American, Native Hawaiian), and reproductive factors among females. Body mass index (BMI, kg/m3) and smoking status (ever, never, current) were included as strata variables due to their proportional hazard violation. Categorical birth year was also included as a strata variable to adjust for possible cohort effects. CI: Confidence Interval; HR: Hazard Ratio; P het: P- heterogeneity for likelihood ratio test for difference in association across covariate levels.
Supplementary Figure S10 from Interethnic Differences in Bladder Cancer Incidence and the Association between Type 2 Diabetes and Bladder Cancer in the Multiethnic Cohort Study
Authors: Bogumil David , Cortessis Victoria K. , Wilkens Lynne R. , Le Marchand Loïc , Haiman Christopher A. , Maskarinec Gertraud , Setiawan Veronica Wendy
Published: May 2023

Supplementary Figure 10: Association between Any T2D and BCA, stratified by race/ethnicity and SEER stage. SEER stage. 0: In situ: noninvasive, intraepithelial; 1: Localized only; 2: Regional by direct extension only; 3: Regional lymph node(s) involved only; 4: Regional by BOTH direct extension AND regional lymph node(s) involved; 5: Regional, NOS; 7: Distant site(s)/lymph node(s) involved; 8: Unknown if extension or metastasis. Models adjusted for pack-years smoked (0, 1-10, 11-20, 21-30, 31-40, >40), alcohol consumption (<1 drinks/month, ≤1 drinks/day, >1 drinks/day), sex (male, female), number of cigarettes smoked per day among smokers (5 cigarettes or less, 6-10 cigarettes, 11-20, 21-30, 31 or more), race/ethnicity (European American, African American, Japanese American, Latin American, Native Hawaiian), and reproductive factors among females. Body mass index (BMI, kg/m3) and smoking status (ever, never, current) were included as strata variables due to their proportional hazard violation. Categorical birthyear was also included as a strata variable to adjust for possible cohort effects. CI: Confidence Interval; HR: Hazard Ratio.
Mulheres Negras no Graffiti e na Pintura: um estudo de caso em Fortaleza-CE
Authors: Dala Jandira Miguel , António Doneta Franciso
Published: May 2023

Neste artigo, procuramos discutir sobre os trabalhos de graffiti e pintura de uma artista urbana a partir de nossas experiências como mulheres negras e pesquisadoras numa universidade pública brasileira. As vivências como bolsistas do Programa Institucional de Bolsas de Iniciação Científica (PIBIC) com a pesquisa intitulada Mulheres e Arte Urbana: resistências na cena de Fortaleza, a partir de questões de gênero intensificadas por raça e classe em processos artísticos, e que foram o foco de nossa problematização. A metodologia usada foi um estudo de caso tendo por base a pesquisa narrativa e observação participante na cidade de Fortaleza (CE) entre os anos de 2019 e 2020. Os principais aportes teóricos utilizados neste texto foram Achille Mbembe (2014), Vera Pallamin (2000), Djamila Ribeiro (2017) e Carla Akotirene (2019).
CIB2 Is a Novel Endogenous Repressor of Atrial Remodeling
Authors: Wang Yihui , Wang Jizheng , Shi Ling , Chen Xiuyu , Li Desheng , Cui Chen , Yang Kai , Lu Minjie , Huang Jinhua , Zhang Lei , Li Fei , Wang Jinxi , Chen Biyi , Wang Bin , Hall Duane D. , Pan Zhenwei , Hong Jiang , Song Long-Sheng , Song Lei , Zhao Shihua
Published: May 2023

Background:

Atrial fibrillation (AF) is a highly prevalent condition that can cause or exacerbate heart failure, is an important risk factor for stroke, and is associated with pronounced morbidity and death. Genes uniquely expressed in the atria are known to be essential for maintaining atrial structure and function. Atrial tissue remodeling contributes to arrhythmia recurrence and maintenance. However, the mechanism underlying atrial remodeling remains poorly understood. This study was designed to investigate whether other uncharacterized atrial specific genes play important roles in atrial physiology and arrhythmogenesis.

Methods:

RNA-sequencing analysis was used to identify atrial myocyte specific and angiotensin II–responsive genes. Genetically modified, cardiomyocyte-specific mouse models (knockout and overexpression) were generated. In vivo and in vitro electrophysiological, histology, and biochemical analyses were performed to determine the consequences of CIB2 (calcium and integrin binding family member 2 protein) gain and loss of function in the atrium.

Results:

Using RNA-sequencing analysis, we identified CIB2 as an atrial-enriched protein that is significantly downregulated in the left atria of patients with AF and mouse models of AF from angiotensin II infusion or pressure overload. Using cardiomyocyte-specific C
ib2
knockout (
Cib2

-/
-

) and atrial myocyte–specific
Cib2
-overexpressing mouse models, we found that loss of C
ib2
enhances AF occurrence, prolongs AF duration, and correlates with a significant increase in atrial fibrosis under stress. Conversely,
Cib2
overexpression mitigates AF occurrence and atrial fibrosis triggered by angiotensin II stress. Mechanistically, we revealed that CIB2 competes with and inhibits CIB1-mediated calcineurin activation, thereby negating stress-induced structural remodeling and AF.

Conclusions:

Our data suggest that CIB2 represents a novel endogenous and atrial-enriched regulator that protects against atrial remodeling and AF under stress conditions. Therefore, CIB2 may represent a new potential target for treating AF.
Ranunculus tengchongensis and R. yanshanensis (Ranunculaceae), both described from Yunnan in China, are merged with R. trigonus
Authors: FEI WEN-QUN , YUAN QIONG , YANG QIN-ER
Published: May 2023

Based on critical observations on herbarium specimens (including type material) and living plants in the wild, we demonstrate that Ranunculus tengchongensis and R. yanshanensis (Ranunculaceae), both described from Yunnan in China, are conspecific with R. trigonus, a species distributed in southwestern China, particularly common in Yunnan province, and somewhat variable with respect to stem indumentum, shape and division of basal leaves, and length of their petioles. We therefore reduce R. tengchongensis and R. yanshanensis to the synonymy of R. trigonus herein.
Taxonomic notes on Camellia crassicolumna and its related species (Theaceae)
Authors: JIANG YIN-ZI , YU XIANG-QIN , ZHANG TAO , PENG HUA , YANG SHI-XIONG
Published: May 2023

Camellia crassicolumna (Theaceae) was described as an endemic species to southeastern Yunnan, China. In the most recent monograph of Camellia, seven names, including C. crispula, C. atrothea, C. makuanica, C. haaniensis, C. purpurea, C. rotundata, and C. crassicolumna var. shangbaensis, were listed as heterotypic synonyms of C. crassicolumna. Our examination of related specimens reveals that the statement ‘ovariis pilosis’ in the protologue of C. crassicolumna is incongruent with its type specimens whose ovaries are glabrous. The morphological traits of C. crassicolumna resemble C. kwangsiensis var. kwangnanica. Therefore, C. crassicolumna is reduced into C. kwangsiensis var. kwangnanica. The species status of C. crispula is reinstated with C. atrothea, C. makuanica, C. haaniensis, C. purpurea, C. rotundata, and C. crassicolumna var. shangbaensis treated as its heterotypic synonyms. A new combination, C. crispula var. multiplex, is proposed, and the lectotype of C. atrothea is designated here.
Four new species of Discomorpha Chevrolat, 1837 (Coleoptera: Chrysomelidae: Cassidinae: Omocerini), with key to Discomorpha s. str.
Authors: BOROWIEC LECH
Published: May 2023

The following new species of Discomorpha s. str. (Coleoptera: Chrysomelidae: Cassidinae) are described: Discomorpha howdenorum sp. nov. (Venezuela), Discomorpha atahualpai sp. nov. (Peru), Discomorpha putamayoensis sp. nov. (Peru), and Discomorpha giganteensis sp. nov. (Colombia). Colour photos of the dorsal and lateral habitus of all new species are provided. A key to the subgenus Discomorpha s. str. is given. Discomorpha nevermanni (Spaeth, 1928) is transferred from the nominotypical subgenus to the subgenus Vulpia Spaeth, 1913.
Two new species of the genus Homogryllacris (Orthoptera: Gryllacrididae) with the male of Homogryllacris irregularis Lu, Zhang & Bian, 2022 from Yunnan, China
Authors: DUAN YANHAO , SU JIE , ZHANG WENXIANG , SHI FUMING
Published: May 2023

This paper reports two new species of the genus Homogryllacris Liu, 2007 from Yunnan, China. In addition, the male of Homogryllacris irregularis Lu, Zhang & Bian, 2022 is described for the first time.
Types of Geoeconomic Power and Competition over Myanmar Before and During the Reform Era of the 2010s
Authors: Oh Yoon Ah
Published: May 2023

Over the past decade, the United States, China, and Japan contested for influence in Myanmar, as the country began to emerge from decades of isolation and military rule. Despite the rich descriptions of rivalries between the United States and China, as well as Japan and China, the nature of geoeconomic power competition in Myanmar remains underarticulated. Popular accounts often use a magnitude-based concept of power to track how much power countries have gained or lost over Myanmar. However, the types of power may be equally important, particularly for understanding the geoeconomic dynamics in play. This article thus examines the geoeconomic power competition in Myanmar using a typology of interstate economic power relations. This typology expands the conventional framework centered on geographic distance to incorporate other types of geoeconomic power, such as deterritorialized financial regulatory power and the adjacent power exercised through shared borders. This approach contributes to a better understanding of the geoeconomic rivalries in Myanmar and across Southeast Asia.
Investigation of the mechanical properties triple periodic minimal surfaces lattice structures with functional graded of porosity
Authors: Emir Ender , Bahçe Erkan
Published: May 2023

In recent years, triple periodic minimal surfaces (TPMS) have attracted attention in many applications such as biomaterials, aerospace, defense industry etc. lightweight components with high strength and functionally graded material (FGM). In particular, the mechanical properties and deformation behavior of these structures under load should be examined. In this study, it was aimed to evaluate the manufacturability and mechanical performance of fixed pore size and functional graded porosity (FGP) lattice structures produced by fused deposition modelling (FDM) method. TPMS primitive and gyroid lattice structures designed in the dimensions of 20 × 20 × 20 mm with fixed 20% pore size and functional graded (FG) from 20% to 40% pore size were used in the experiments. In order to reveal the effects of pore size on mechanical performance, uniaxial compression tests were carried out. In addition, for the validation of the experimental results, compression tests with the finite element method (FEM) were simulated for each sample. In the two different pore size changes tested in the study, the gyroid lattice structure showed the highest mechanical performance compared to the primitive lattice structure. In addition, the FEM results were in good agreement with the experimental results.
Can Machiavellianism Not be Prosocial? Roles of Empathy and Death Anxiety
Authors: Fan Qiujun , Wang Xuezhen , Liu Yanan
Published: May 2023

Machiavellianism has always been notorious, as it is egotistical and manipulative. This study aims to explore whether Machiavellian individuals would increase prosocial behavior to buffer death anxiety, based on Terror Management Theory. A total of 420 Chinese volunteers completed a survey regarding Machiavellianism, empathy (cognitive empathy, affective empathy), death anxiety, and prosocial behavior tendencies. The results indicated that affective empathy mediated the relationship between Machiavellianism and some types of prosocial behavior (total, altruistic, anonymous, compliant, dire and emotional), and the mediating effect was moderated by death anxiety. This finding revealed that although individuals with high levels of Machiavellianism were supposed to be callous, when suffering from death anxiety, they became more affective-empathetic, and thus more prosocial. Our study enriches the relationship between Machiavellianism and kindness.
Provision of Postpartum Contraception Before and After the Start of the COVID-19 Pandemic in Maine
Authors: Gelsinger Catherine , Palmsten Kristin , Lipkind Heather S. , Pfeiffer Mariah , Ackerman-Banks Christina , Hutcheon Jennifer A. , Ahrens Katherine A.
Published: May 2023

Objective:

Preliminary findings from selected health systems revealed interruptions in reproductive health care services due to the COVID-19 pandemic. We estimated changes in postpartum contraceptive provision associated with the start of the COVID-19 pandemic in Maine.

Methods:

We used the Maine Health Data Organization’s All Payer Claims Database for deliveries from October 2015 through March 2021 (n = 45 916). Using an interrupted time-series analysis design, we estimated changes in provision rates of long-acting reversible contraception (LARC), permanent contraception, and moderately effective contraception within 3 and 60 days of delivery after the start of the COVID-19 pandemic. We performed 6- and 12-month analyses (April 2020–September 2020, April 2020–March 2021) as compared with the reference period (October 2015–March 2020). We used Poisson regression models to calculate level-change rate ratios (RRs) and 95% CIs.

Results:

The 6-month analysis found that provision of LARC (RR = 1.89; 95% CI, 1.76-2.02) and moderately effective contraception (RR = 1.51; 95% CI, 1.33-1.72) within 3 days of delivery increased at the start of the COVID-19 pandemic, while provision of LARC (RR = 0.95; 95% CI, 0.93-0.97) and moderately effective contraception (RR = 1.08; 95% CI, 1.05-1.11) within 60 days of delivery was stable. Rates of provision of permanent contraception within 3 days (RR = 0.70; 95% CI, 0.63-0.78) and 60 days (RR = 0.71; 95% CI, 0.63-0.80) decreased. RRs from the 12-month analysis were generally attenuated.

Conclusion:

Disruptions in postpartum provision of permanent contraception occurred at the beginning of the COVID-19 pandemic in Maine. Public health policies should include guidance for contraceptive provision during public health emergencies and consider designating permanent contraception as a nonelective procedure.
A Maturity Model for Content Strategy Development and Technical Communicator Leadership
Authors: Campbell Kim Sydow , Swisher Val
Published: May 2023

While technical communication consultants and researchers agree that content strategy requires attention to both customer needs and business goals, we found no evidence that technical communication educators promote an accurate understanding of business goals among their content strategy students. Through industry–academia collaboration, we integrate two existing models, using content tactics within organizational characteristics that define the maturity level of an organization's content operations. Analyzing the current state of maturity for each characteristic highlights gaps that can define a content strategy with prioritized tactics and, ultimately, encourages the growth of technical communicator leadership and the empowerment of our profession.