bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnesium Compounds Increase Aquaporin‐3 in Human Epidermal Keratinocyte HaCaT Cells
Authors: Ikarashi Nobutomo , Kawai Haruka , Shinozaki Yui , Tabata Keito , Yoshida Ryotaro , Nishinaka Yui , Kon Risako , Sakai Hiroyasu , Hosoe Tomoo
Published: June 2023

Several studies have shown that magnesium can be a useful tool in preventing various skin disorders. However, the mechanism remains unclear. In this study, we analyzed the mechanism by which magnesium improves skin function, focusing on the water channel aquaporin‐3 (AQP3), which is a cutaneous functional molecule. Magnesium compounds (magnesium acetate, magnesium chloride, magnesium sulfate, and magnesium lactate) were added to human epidermal keratinocyte HaCaT cells, and the mRNA and protein expression levels of AQP3 were analyzed. We also investigated the mechanism by which magnesium acetate regulates AQP3 expression. Several magnesium compounds were individually added to HaCaT cells, and 6 hours later, the AQP3 mRNA expression level in the treated cells was significantly increased compared to that in the control cells. Among the magnesium compounds, magnesium acetate had a strong effect and markedly increased the AQP3 mRNA expression level by approximately 3.5 times and the protein expression level by approximately 3 times. Magnesium acetate also enhanced the phosphorylation of cAMP response element‐binding protein (CREB), which is involved in AQP3 transcription. Furthermore, the increase in AQP3 expression levels induced by magnesium acetate was suppressed by treatment with the protein kinase A (PKA) inhibitor H‐89. Magnesium compounds increased the expression level of AQP3 in epidermal keratinocytes and may have a skin‐moisturizing effect. The magnesium‐induced phosphorylation of CREB may be associated with the activation of the cAMP/PKA pathway. Overall, magnesium compounds may be useful for the prevention and treatment of age‐associated xeroderma.
Figure S1 Summary of the keywords provided by authors of the original articles included in the review. from A Review of the Application of Spatial Survival Methods in Cancer Research: Trends, Modeling, and Visualization Techniques
Authors: Bizuayehu Habtamu Mellie , Cameron Jessica K. , Dasgupta Paramita , Baade Peter D.
Published: June 2023

Supplementary Figure S1 shows summary of keywords extracted from articles
Supplementary Table 9 from Sleep Behaviors, Genetic Predispositions, and Risk of Esophageal Cancer
Authors: Wang Xiaoyan , Tian Ruiyi , Zong Xiaoyu , Jeon Myung Sik , Luo Jingqin , Colditz Graham A. , Wang Jean S. , Tsilidis Konstantinos K. , Ju Yo-El S. , Govindan Ramaswamy , Puri Varun , Cao Yin
Published: June 2023

Supplementary Table 9 shows the additive interaction between composite sleep score and genetic risk with EAC risk
Supplementary Table 8 from Sleep Behaviors, Genetic Predispositions, and Risk of Esophageal Cancer
Authors: Wang Xiaoyan , Tian Ruiyi , Zong Xiaoyu , Jeon Myung Sik , Luo Jingqin , Colditz Graham A. , Wang Jean S. , Tsilidis Konstantinos K. , Ju Yo-El S. , Govindan Ramaswamy , Puri Varun , Cao Yin
Published: June 2023

Supplementary Table 8 shows the joint associations between composite sleep score and genetic risk with EAC risk
Supplementary Table 7 from Sleep Behaviors, Genetic Predispositions, and Risk of Esophageal Cancer
Authors: Wang Xiaoyan , Tian Ruiyi , Zong Xiaoyu , Jeon Myung Sik , Luo Jingqin , Colditz Graham A. , Wang Jean S. , Tsilidis Konstantinos K. , Ju Yo-El S. , Govindan Ramaswamy , Puri Varun , Cao Yin
Published: June 2023

Supplementary Table 7 shows the association between composite sleep score and EAC risk by BMI group
Supplementary Table 2 from Sleep Behaviors, Genetic Predispositions, and Risk of Esophageal Cancer
Authors: Wang Xiaoyan , Tian Ruiyi , Zong Xiaoyu , Jeon Myung Sik , Luo Jingqin , Colditz Graham A. , Wang Jean S. , Tsilidis Konstantinos K. , Ju Yo-El S. , Govindan Ramaswamy , Puri Varun , Cao Yin
Published: June 2023

Supplementary Table 2 shows the weights used to construct the weighted sleep score
Supplementary Table 1 from Folate Intake and Ovarian Cancer Risk among Women with Endometriosis: A Case–Control Study from the Ovarian Cancer Association Consortium
Authors: Gersekowski Kate , Ibiebele Torukiri I , Doherty Jennifer A. , Harris Holly R. , Goodman Marc T. , Terry Kathryn L. , Wu Anna H. , Bandera Elisa V. , Qin Bo , Ong Jue-Sheng , Tyrer Jonathan P. , Dixon-Suen Suzanne C. , Modugno Francesmary , Risch Harvey A , Webb Penelope M.
Published: June 2023

Supplementary Table 1 shows the range of folate intake included in each tertile, by OCAC study site.
Table S2 from Field Synopsis of Environmental and Genetic Risk Factors of Sporadic Early-Onset Colorectal Cancer and Advanced Adenoma
Authors: Zhang Rongqi , Boakye Daniel , Yang Nan , Zhou Xuan , Zhou Yajing , Jiang Fangyuan , Yu Lili , Wang Lijuan , Sun Jing , Yuan Shuai , Chen Jie , Hamilton Ashleigh C. , Coleman Helen G. , Larsson Susanna C. , Little Julian , Dunlop Malcolm G. , Giovannucci Edward L. , Theodoratou Evropi , Li Xue
Published: June 2023

Supplementary Table 2 shows the quality rating of the included studies.
Table S1 from Field Synopsis of Environmental and Genetic Risk Factors of Sporadic Early-Onset Colorectal Cancer and Advanced Adenoma
Authors: Zhang Rongqi , Boakye Daniel , Yang Nan , Zhou Xuan , Zhou Yajing , Jiang Fangyuan , Yu Lili , Wang Lijuan , Sun Jing , Yuan Shuai , Chen Jie , Hamilton Ashleigh C. , Coleman Helen G. , Larsson Susanna C. , Little Julian , Dunlop Malcolm G. , Giovannucci Edward L. , Theodoratou Evropi , Li Xue
Published: June 2023

Supplementary Table 1 shows basic characteristic of the included studies.
Data from Development and Demonstration of Tobacco Treatment Measures for Cancer Registries:
Novel Metrics for Quality Improvement
Authors: Hutcheson Tresza D. , Metcalf Tim , Ellerbeck Edward F. , Sanderson Cox Lisa , Hu Jinxiang , Chen Xi , Richter Kimber P.
Published: June 2023

Abstract
Background. Individuals undergoing cancer treatment have better outcomes when they discontinue tobacco use. Few cancer centers systematically provide evidence-based cessation services. As part of a national quality improvement initiative (Cancer Center Cessation Initiative, (C3i)), we collaborated with our cancer registry to develop and implement two tobacco treatment metrics for tracking the provision of behavioral support and pharmacotherapy.
Methods. Post-development, the tobacco treatment metrics were integrated into the registry for all future patients. We used means and frequencies to summarize tobacco treatment for cases treated between 2017-2019, coinciding with the timeframe of C3i participation.
Results. Of 17,735 cancer cases reviewed, both measures were captured on 17,654 (99.5%) of patients, with 3,091 (17.4%) identified as users of tobacco. Across the 3 years, 557 (18%) of individuals who used tobacco received either tobacco cessation pharmacotherapy or behavioral support; with 478 (15.5%) receiving behavioral counseling, 352 (11.4%) receiving pharmacotherapy, and 273 (8.8%) receiving both—considered gold standard care. Tobacco treatment varied substantially across cancer types. The odds of receiving gold standard care were 2.37 times greater in 2019 compared to 2017. (OR=2.37, 95% CI=1.63–3.46, p<0.0001).
Conclusions. The new metrics demonstrated high completion rates and their potential to track quality improvement efforts over time. They identified suboptimal treatment reach, but a potential increase in treatment over time and greater treatment among tobacco-related versus non-tobacco-related cancers.
Impact. Continued tobacco use worsens cancer care outcomes. Integrating measures into cancer registries is a viable option for tracking tobacco treatment and cessation in the context of cancer care.
Data from Pre-diagnostic 25-hydroxyvitamin D in association with cancer specific- and all-cause mortality among low income, non-Hispanic Black Americans with colorectal cancer
Authors: Lawler Thomas P. , Khankari Nikhil K. , Shu Xiao-Ou , Steinwandel Mark , Cai Qiuyin , Jurutka Peter W. , Zheng Wei , Warren Andersen Shaneda
Published: June 2023

Abstract
Background: Observational studies show high pre-diagnosis 25-hydroxyvitamin D is associated with lower mortality after colorectal cancer (CRC) diagnosis. Results from clinical trials suggest vitamin D supplementation may improve outcomes among CRC patients. Most studies included few Black Americans, who typically have lower 25-hydroxyvitamin D. We evaluated associations between serum 25-hydroxyvitamin D and mortality after CRC diagnosis among Black American cases.

Methods: Data arose from 218 Black Americans from the Southern Community Cohort Study diagnosed with CRC during follow-up (age 40-79 at enrollment). Pre-diagnostic 25-hydroxyvitamin D was measured at enrollment and categorized as deficient (<12 ng/mL), insufficient (12-19.9 ng/mL), or sufficient (≥20 ng/mL). Mortality was determined from the National Death Index. Cox proportional hazards were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between 25-hydroxyvitamin D and mortality.

Results: As a continuous exposure, higher 25-hydroxyvitamin D was associated with overall mortality (HR=0.79 [0.65-0.96] per standard deviation increase, p-trend =.02) and CRC-specific mortality (HR=0.83 [0.64-1.08], p-trend =.16). For overall mortality, associations were strongest among females (HR=0.65 [0.42-0.92]), current smokers (HR=0.61 [0.38-0.98]), and obese participants (HR=0.47 [0.29-0.77]). Compared to those with deficiency, participants with sufficient 25-hydroxyvitamin D had lower overall mortality after multivariable adjustment (HR: 0.61 [0.37-1.01]).

Conclusions: Pre-diagnosis 25-hydroxyvitamin D is inversely associated with overall and CRC-specific mortality among Black Americans with CRC. Correcting vitamin D deficiency may improve survival of these patients, particularly for obese individuals and smokers.

Impact: Our results support including more Black Americans in trials of vitamin D supplementations to improve CRC outcomes.
Association between Sleep Duration and Colorectal Adenomas: Findings from a Case–Control Study in Vietnam
Authors: Tran Chi Thi-Du , Paragomi Pedram , Tran Mo Thi , Nguyen Mai Vu-Tuyet , Tuong Thuy Thi-Van , Tran Quang Hong , Le Linh Cu , Pham Huong Thi-Thu , Ha Hien Thi-Thu , Bui Nam Chi , Vu Hien Huy , Ta Phuong Que , Shrubsole Martha J. , Cai Qiuyin , Ye Fei , Le Song Huu , Vu Khien Van , Tran Huong Thi-Thanh , Tran Thuan Van , Boffetta Paolo , Shu Xiao-Ou , Luu Hung N.
Published: June 2023

Background:

Colorectal cancer is one of the leading cancers worldwide and in Vietnam. Adenomas are important precursors of colorectal cancer. Study on the association between sleep duration and development of colorectal adenoma (CRA) is limited, particularly among Vietnamese population.

Methods:

We conducted an individually matched case–control study of 870 CRA cases and 870 controls in a large-scale colorectal screening program involving 103,542 individuals ages ≥40 years old in Hanoi, Vietnam. Sleep duration was categorized in three groups: short: ≤6 hours/day, normal: 7 to 8 hours/day, and long: >8 hours/day. Conditional logistic regression was used to evaluate the association between sleep duration and adenomas risk after controlling for potential confounders.

Results:

Overall, short-sleep duration was associated with increased risk of having CRA compared with normal duration [OR, 1.48; 95% confidence interval (CI), 1.12–1.97]. This pattern was present in both females (OR, 1.58; 95% CI, 1.14–2.18) and males (OR, 1.45; 95% CI, 1.08–1.93), with advanced adenomas (OR, 1.61; 95% CI, 1.09–2.38) and non-advanced adenomas (OR, 1.66; 95% CI, 1.19–2.32). Furthermore, the association between CRA development and short-sleep duration was more apparent among females who were nondrinker, nonobese, physically active, with proximal or both sided adenomas and with cardiometabolic disorder. Among males, the short-sleep duration was associated with CRA risk among never-smoking, cardiometabolic disorders, and obese.

Conclusions:

Short-sleep duration was associated with increased prevalence of both advanced and non-advanced CRAs among Vietnamese population.

Impact:

Findings from this study showed that maintaining an adequate sleep duration may have an important implication for colorectal adenoma prevention and control.
Table S1 from Fibronectin Contributes to a BRAF Inhibitor–driven Invasive Phenotype in Thyroid Cancer through EGR1, Which Can Be Blocked by Inhibition of ERK1/2
Authors: Hicks Hannah M. , Pozdeyev Nikita , Sams Sharon B. , Pugazhenthi Umarani , Bales Elise S. , Hofmann Marie-Claude , McKenna Logan R. , Schweppe Rebecca E.
Published: June 2023

Table S1. Thyroid cancer cell lines and their sensitivity/resistance to BRAFi.
Figure S8 from Fibronectin Contributes to a BRAF Inhibitor–driven Invasive Phenotype in Thyroid Cancer through EGR1, Which Can Be Blocked by Inhibition of ERK1/2
Authors: Hicks Hannah M. , Pozdeyev Nikita , Sams Sharon B. , Pugazhenthi Umarani , Bales Elise S. , Hofmann Marie-Claude , McKenna Logan R. , Schweppe Rebecca E.
Published: June 2023

Figure S8. The effects of EGR1 depletion on signaling responses to BRAF inhibition and invasion.
Figure S3 from Fibronectin Contributes to a BRAF Inhibitor–driven Invasive Phenotype in Thyroid Cancer through EGR1, Which Can Be Blocked by Inhibition of ERK1/2
Authors: Hicks Hannah M. , Pozdeyev Nikita , Sams Sharon B. , Pugazhenthi Umarani , Bales Elise S. , Hofmann Marie-Claude , McKenna Logan R. , Schweppe Rebecca E.
Published: June 2023

Figure S3. Sensitivity to BRAF inhibition does not correlate with fibronectin, α5β1 integrin, c-MET, or FAK/Src levels. BRAF inhibition increases fibronectin expression and secretion, which is blocked by ERK1/2 inhibition.
Chromatin-Associated SIN3B Protects Cancer Cells from Genotoxic Stress-Induced Apoptosis and Dictates DNA Damage Repair Pathway Choice
Authors: Morales-Valencia Jorge , Petit Coralie , Calderon Alexander , Saini Siddharth , David Gregory
Published: June 2023

Transcription and DNA damage repair act in a coordinated manner. The scaffolding protein SIN3B serves as a transcriptional co-repressor of hundreds of cell cycle–related genes. However, the contribution of SIN3B during the DNA damage response remains unknown. Here, we show that SIN3B inactivation delays the resolution of DNA double-strand breaks and sensitizes cancer cells to DNA-damaging agents, including the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, SIN3B is rapidly recruited to DNA damage sites where it directs the accumulation of Mediator of DNA Damage Checkpoint 1 (MDC1). In addition, we show that SIN3B inactivation favors the engagement of the alternative nonhomologous end joining (NHEJ) repair pathway over the canonical NHEJ. Altogether, our findings impute an unexpected function for the transcriptional co-repressor SIN3B as a gatekeeper of genomic integrity and a determining factor in the DNA repair choice pathway, and point to the inhibition of the SIN3B chromatin-modifying complex as a novel therapeutic vulnerability in cancer cells.

Implications:

Identifying SIN3B as a modulator of DNA damage repair choice provides novel potential therapeutic avenues to sensitize cancer cells to cytotoxic therapies.
Targeting the ATF6-Mediated ER Stress Response and Autophagy Blocks Integrin-Driven Prostate Cancer Progression
Authors: Macke Amanda J. , Pachikov Artem N. , Divita Taylor E. , Morris Mary E. , LaGrange Chad A. , Holzapfel Melissa S. , Kubyshkin Anatoly V. , Zyablitskaya Evgeniya Y. , Makalish Tatiana P. , Eremenko Sergey N. , Qiu Haowen , Riethoven Jean-Jack M. , Hemstreet George P. , Petrosyan Armen
Published: June 2023

Prostate cancer progression to the lethal metastatic castration-resistant phenotype (mCRPC) is driven by αv integrins and is associated with Golgi disorganization and activation of the ATF6 branch of unfolded protein response (UPR). Overexpression of integrins requires N-acetylglucosaminyltransferase-V (MGAT5)-mediated glycosylation and subsequent cluster formation with Galectin-3 (Gal-3). However, the mechanism underlying this altered glycosylation is missing. For the first time, using HALO analysis of IHC, we found a strong association of integrin αv and Gal-3 at the plasma membrane (PM) in primary prostate cancer and mCRPC samples. We discovered that MGAT5 activation is caused by Golgi fragmentation and mislocalization of its competitor, N-acetylglucosaminyltransferase-III, MGAT3, from Golgi to the endoplasmic reticulum (ER). This was validated in an ethanol-induced model of ER stress, where alcohol treatment in androgen-refractory PC-3 and DU145 cells or alcohol consumption in patient with prostate cancer samples aggravates Golgi scattering, activates MGAT5, and enhances integrin expression at PM. This explains known link between alcohol consumption and prostate cancer mortality. ATF6 depletion significantly blocks UPR and reduces the number of Golgi fragments in both PC-3 and DU145 cells. Inhibition of autophagy by hydroxychloroquine (HCQ) restores compact Golgi, rescues MGAT3 intra-Golgi localization, blocks glycan modification via MGAT5, and abrogates delivery of Gal-3 to the cell surface. Importantly, the loss of Gal-3 leads to reduced integrins at PM and their accelerated internalization. ATF6 depletion and HCQ treatment synergistically decrease integrin αv and Gal-3 expression and temper orthotopic tumor growth and metastasis.

Implications:

Combined ablation of ATF6 and autophagy can serve as new mCRPC therapeutic.
Supplementary Table 9 from Associations between Physical Activity and Incidence of Cancer among Overweight Adults in Korea: Results from the Health Examinees-G Study
Authors: Choi Jaesung , Park JooYong , Kim Ji-Eun , Lee Miyoung , Kang Daehee , Shin Aesun , Choi Ji-Yeob
Published: June 2023

Supplementary Table 9 shows the association of physical activity with gastric cancer incidence
Supplementary Table 2 from Associations between Physical Activity and Incidence of Cancer among Overweight Adults in Korea: Results from the Health Examinees-G Study
Authors: Choi Jaesung , Park JooYong , Kim Ji-Eun , Lee Miyoung , Kang Daehee , Shin Aesun , Choi Ji-Yeob
Published: June 2023

Supplementary Table 2 shows the association of physical activity with overall cancer incidence after excluding those diagnosed with cancer within the first 2 years of follow-up
Supplementary Table 17 from Associations between Physical Activity and Incidence of Cancer among Overweight Adults in Korea: Results from the Health Examinees-G Study
Authors: Choi Jaesung , Park JooYong , Kim Ji-Eun , Lee Miyoung , Kang Daehee , Shin Aesun , Choi Ji-Yeob
Published: June 2023

Supplementary Table 17 shows the association of physical activity with 13 obesity-related cancers incidence
Supplementary Methods from Mitophagy Promotes Resistance to BH3 Mimetics in Acute Myeloid Leukemia
Authors: Glytsou Christina , Chen Xufeng , Zacharioudakis Emmanouil , Al-Santli Wafa , Zhou Hua , Nadorp Bettina , Lee Soobeom , Lasry Audrey , Sun Zhengxi , Papaioannou Dimitrios , Cammer Michael , Wang Kun , Zal Tomasz , Zal Malgorzata Anna , Carter Bing Z. , Ishizawa Jo , Tibes Raoul , Tsirigos Aristotelis , Andreeff Michael , Gavathiotis Evripidis , Aifantis Iannis
Published: June 2023

Supplementary Methods, Tables, and References
Data from Mitophagy promotes resistance to BH3 mimetics in acute myeloid leukemia
Authors: Glytsou Christina , Chen Xufeng , Zacharioudakis Emmanouil , Al-Santli Wafa , Zhou Hua , Nadorp Bettina , Lee Soobeom , Lasry Audrey , Sun Zhengxi , Papaioannou Dimitrios , Cammer Michael , Wang Kun , Zal Tomasz , Zal Malgorzata Anna. , Carter Bing Z. , Ishizawa Jo , Tibes Raoul , Tsirigos Aristotelis , Andreeff Michael , Gavathiotis Evripidis , Aifantis Iannis
Published: June 2023

Abstract
BH3-mimetics are used as an efficient strategy to induce cell death in several blood malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 antagonist, is used clinically in combination with hypomethylating agents for the treatment of AML. Moreover, MCL-1 or dual BCL-2/BCL-xL antagonists are under investigation. Yet, resistance to single or combinatorial BH3-mimetics therapies eventually ensues. Integration of multiple genome-wide CRISPR/Cas9 screens revealed that loss of mitophagy modulators sensitizes AML cells to various BH3-mimetics targeting different BCL-2 family members. One such regulator is MFN2, whose protein levels positively correlate with drug resistance in patients with AML. MFN2 overexpression is sufficient to drive resistance to BH3-mimetics in AML. Insensitivity to BH3-mimetics is accompanied by enhanced mitochondria-endoplasmic reticulum interactions and augmented mitophagy flux which acts as a pro-survival mechanism to eliminate mitochondrial damage. Genetic or pharmacologic MFN2 targeting synergizes with BH3-mimetics by impairing mitochondrial clearance and enhancing apoptosis in AML.
Supplementary Tables S1, S2, S5-S13 from The Polyamine–Hypusine Circuit Controls an Oncogenic Translational Program Essential for Malignant Conversion in MYC-Driven Lymphoma
Authors: Nakanishi Shima , Li Jiannong , Berglund Anders E. , Kim Youngchul , Zhang Yonghong , Zhang Ling , Yang Chunying , Song Jinming , Mirmira Raghavendra G. , Cleveland John L.
Published: June 2023

Supplementary Tables S1, S2, S5-S13 includes Supplementary Tables S1, S2, S5-S13.
Supplementary Table S1 provides a summary of BL and DHL patient demographics for the immunohistochemistry study presented in Fig. 1, E and F.
Supplementary Table S2 lists the MYC-dysregulated genes whose expression is significantly altered following depletion of eIF5A or DHPS, related to Fig. 4F.
Supplementary Table S5 shows DHPS GISTIC count and survival of select TCGA PanCancer datasets, related to Fig. 7J.
Supplementary Table S6 shows the genetic mouse models used in this study, related to Methods.
Supplementary Table S7 shows the mouse and human cell lines used in this study, related to Methods.
Supplementary Table S8 lists the antibodies used in this study, related to Methods.
Supplementary Table S9 lists reagents used in this study, related to Methods.
Supplementary Table S10 summarizes the plasmids used in this study, related to Methods.
Supplementary Table S11 lists the sequences of the oligonucleotides used in this study, related to Methods.
Supplementary Table S12 lists accession numbers and publicly deposited data from this study, related to Methods.
Supplementary Table S13 lists software and algorithms used in this study, related to Methods.
Supplementary Figures S1-S7 from The Polyamine–Hypusine Circuit Controls an Oncogenic Translational Program Essential for Malignant Conversion in MYC-Driven Lymphoma
Authors: Nakanishi Shima , Li Jiannong , Berglund Anders E. , Kim Youngchul , Zhang Yonghong , Zhang Ling , Yang Chunying , Song Jinming , Mirmira Raghavendra G. , Cleveland John L.
Published: June 2023

Supplementary Figures S1-S7 includes Supplementary Figure S1-S7 and the figure legend for each figure.
Supplementary Fig. S1 shows that the polyamine-hypusine circuit is activated in many human cancers including MYC-driven lymphoma. Supplementary Fig. S1 is related to Fig. 1.
Supplementary Fig. S2 shows that inhibition of DHPS enzyme activity, or silencing eIF5A or DHPS, suppresses the growth of mouse MYC-driven lymphoma. Supplementary Fig. S2 is related to Fig. 2.
Supplementary Fig. S3 shows that hypusinated eIF5A (eIF5AHyp) contributes to the tumorigenic potential and maintenance of MYC-driven lymphoma. Supplementary Fig. S3 is related to Fig. 3.
Supplementary Fig. S4 shows the effects of eIF5A or DHPS depletion on the transcriptional landscape of MYC-driven lymphoma. Supplementary Fig. S4 is related to Fig. 4.
Supplementary Fig. S5 shows that depletion of eIF5A or DHPS impairs the translation efficiency of subsets of mRNA in MYC-driven lymphoma. Supplementary Fig. S5 is related to Fig. 5.
Supplementary Fig. S6 shows the validation of select eIF5AHyp translation targets identified by the multi-omics analyses, and that the translation of key regulatory cell cycle factors is controlled by hypusinated eIF5A. Supplementary Fig. S6 is related to Fig. 6.
Supplementary Fig. S7 shows that hypusinated eIF5A is essential for the development of MYC-driven lymphoma. Supplementary Fig. S7 is related to Fig. 7.
Data from The polyamine-hypusine circuit controls an oncogenic translational program essential for malignant conversion in MYC-driven lymphoma
Authors: Nakanishi Shima , Li Jiannong , Berglund Anders E. , Kim Youngchul , Zhang Yonghong , Zhang Ling , Yang Chunying , Song Jinming , Mirmira Raghavendra G. , Cleveland John L.
Published: June 2023

Abstract
The MYC oncoprotein is activated in a broad spectrum of human malignancies and transcriptionally reprograms the genome to drive cancer cell growth. Given this, it is unclear if targeting a single effector of MYC will have therapeutic benefit. MYC activates the polyamine-hypusine circuit, which post-translationally modifies the eukaryotic translation factor eIF5A. The roles of this circuit in cancer are unclear. Here we report essential intrinsic roles for hypusinated eIF5A in the development and maintenance of MYC-driven lymphoma, where loss of eIF5A hypusination abolishes malignant transformation of MYC-overexpressing B cells. Mechanistically, integrating RNA-seq, Ribo-seq and proteomic analyses revealed that efficient translation of select targets is dependent upon eIF5A hypusination, including regulators of G1-to-S phase cell cycle progression and DNA replication. This circuit thus controls MYC’s proliferative response, and it is also activated across multiple malignancies. These findings suggest the hypusine circuit as a therapeutic target for several human tumor types.
Data from The Polyamine–Hypusine Circuit Controls an Oncogenic Translational Program Essential for Malignant Conversion in MYC-Driven Lymphoma
Authors: Nakanishi Shima , Li Jiannong , Berglund Anders E. , Kim Youngchul , Zhang Yonghong , Zhang Ling , Yang Chunying , Song Jinming , Mirmira Raghavendra G. , Cleveland John L.
Published: June 2023

Abstract
The MYC oncoprotein is activated in a broad spectrum of human malignancies and transcriptionally reprograms the genome to drive cancer cell growth. Given this, it is unclear if targeting a single effector of MYC will have therapeutic benefit. MYC activates the polyamine–hypusine circuit, which posttranslationally modifies the eukaryotic translation factor eIF5A. The roles of this circuit in cancer are unclear. Here we report essential intrinsic roles for hypusinated eIF5A in the development and maintenance of MYC-driven lymphoma, where the loss of eIF5A hypusination abolishes malignant transformation of MYC-overexpressing B cells. Mechanistically, integrating RNA sequencing, ribosome sequencing, and proteomic analyses revealed that efficient translation of select targets is dependent upon eIF5A hypusination, including regulators of G1–S phase cell-cycle progression and DNA replication. This circuit thus controls MYC's proliferative response, and it is also activated across multiple malignancies. These findings suggest the hypusine circuit as a therapeutic target for several human tumor types.
Significance:
Elevated EIF5A and the polyamine–hypusine circuit are manifest in many malignancies, including MYC-driven tumors, and eIF5A hypusination is necessary for MYC proliferative signaling. Not­ably, this circuit controls an oncogenic translational program essential for the development and maintenance of MYC-driven lymphoma, supporting this axis as a target for cancer prevention and treatment.

See related commentary by Wilson and Klein.
Figure S6 from Mitochondria Transfer from Mesenchymal Stem Cells Confers Chemoresistance to Glioblastoma Stem Cells through Metabolic Rewiring
Authors: Nakhle Jean , Khattar Khattar , Özkan Tülin , Boughlita Adel , Abba Moussa Daouda , Darlix Amélie , Lorcy Frédérique , Rigau Valérie , Bauchet Luc , Gerbal-Chaloin Sabine , Daujat-Chavanieu Martine , Bellvert Floriant , Turchi Laurent , Virolle Thierry , Hugnot Jean-Philippe , Buisine Nicolas , Galloni Mireille , Dardalhon Valérie , Rodriguez Anne-Marie , Vignais Marie-Luce
Published: June 2023

Metabolite detection in resected GBM from 8 patients, at 1rst resection and at 2nd resection post-TMZ treatment. For each metabolite, the C12/C13 ratios normalized to tissue protein concentrations are indicated.
Figure S1 from Mitochondria Transfer from Mesenchymal Stem Cells Confers Chemoresistance to Glioblastoma Stem Cells through Metabolic Rewiring
Authors: Nakhle Jean , Khattar Khattar , Özkan Tülin , Boughlita Adel , Abba Moussa Daouda , Darlix Amélie , Lorcy Frédérique , Rigau Valérie , Bauchet Luc , Gerbal-Chaloin Sabine , Daujat-Chavanieu Martine , Bellvert Floriant , Turchi Laurent , Virolle Thierry , Hugnot Jean-Philippe , Buisine Nicolas , Galloni Mireille , Dardalhon Valérie , Rodriguez Anne-Marie , Vignais Marie-Luce
Published: June 2023

Experimental design and timeline
FIGURE 7 from Mitochondria Transfer from Mesenchymal Stem Cells Confers Chemoresistance to Glioblastoma Stem Cells through Metabolic Rewiring
Authors: Nakhle Jean , Khattar Khattar , Özkan Tülin , Boughlita Adel , Abba Moussa Daouda , Darlix Amélie , Lorcy Frédérique , Rigau Valérie , Bauchet Luc , Gerbal-Chaloin Sabine , Daujat-Chavanieu Martine , Bellvert Floriant , Turchi Laurent , Virolle Thierry , Hugnot Jean-Philippe , Buisine Nicolas , Galloni Mireille , Dardalhon Valérie , Rodriguez Anne-Marie , Vignais Marie-Luce
Published: June 2023

Metabolomics analysis of resected GBM from patients, pre- and post-TMZ treatment shows increased nucleotides concentrations. A, Metabolomics analysis were performed on GBM resected tumors from 8 patients, before treatment and after radiotherapy and several cycles (3 to 13) of TMZ treatment. B, MRI profiles and H&E-stained tissue sections of the analyzed GBM tumors, before and after TMZ treatment. Tumor areas at first and second resections are framed. Scale bar, 100 μm. C, Mass spectrometry metabolomics analysis of the resected GBM. The C12/C13 metabolite ratios normalized to tissue protein concentrations are indicated. Out of the 8 patients, 6 followed a similar trend (solid lines), while 2 followed an opposite trend (dotted lines). Statistical analysis by ratio paired Student t test (AMP, GMP, UMP) and Wilcoxon matched-pairs signed-rank test (CMP) on metabolomics data from the 6 patients.
Transtorno de Ansiedade Generalizada em universitários brasileiros durante a pandemia de COVID-19
Authors: Soares Fernanda Farias , Brilhante Andreia Fernandes , Cruz Andrey Oliveira da , Sinhorin Gustavo Henrique , Sinhorin Géssica Thais , Cruz Jene Greyce Oliveira da , Lago Rozilaine Redi , Brandt Marisol de Paula Reis , Melchior Leonardo Augusto Kohara
Published: June 2023

Objetivo: este estudo avaliou os níveis de ansiedade de universitários brasileiros durante a pandemia de COVID-19. Metodologia: a escala de Transtorno de Ansiedade Generalizada de 7 itens foi usada para medir os níveis de ansiedade de 1.837 respondentes a um questionário de pesquisa online. Resultados: os participantes foram em sua maioria mulheres de 18 a 27 anos, matriculados em programas de pós-graduação em universidades públicas, morando com pessoas consideradas de risco para COVID-19, e com renda familiar de 1 a 3 salários mínimos. Mais de 75% dos participantes relataram algum nível de ansiedade, com 23,08% relatando níveis graves, enquanto apenas 24,93% apresentaram níveis normais de ansiedade. A regressão logística ordinal identificou que ser mulher jovem de baixa renda pode afetar o nível de ansiedade. Além disso, estudantes da área de humanidades, estudantes bem informados e aqueles em risco de COVID-19 eram significativamente mais propensos a sentir ansiedade. Conclusão: a saúde mental dos universitários brasileiros, particularmente de determinados grupos, foi afetada pela pandemia de COVID-19 e requer atenção e cuidados específicos.
Myocardial Flow Assessment After Heart Transplantation Using Dynamic Cadmium-Zinc-Telluride Single-Photon Emission Computed Tomography With
201
Tl and
99m
Tc Tracers and Validated by
13
N-NH
3
Positron Emission Tomography
Authors: Ko Kuan-Yin , Ko Chi-Lun , Lee Chii-Ming , Cheng Ju-Shin , Wu Yen-Wen , Hsu Ron-Bin , Chen Yih-Sharng , Wang Shoei-Shen , Yen Ruoh-Fang , Cheng Mei-Fang
Published: June 2023

Background:

Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse form of vasculopathy and is the most common cause of long-term cardiovascular mortality in heart transplant patients. This study aimed to investigate the diagnostic performance of
99m
Tc and
201
Tl tracers in the assessment of CAV using cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) for myocardial blood flow (MBF) and myocardial flow reserve (MFR) quantification, which was further validated using
13
N-NH
3
positron emission tomography (PET).

Methods:

Thirty-eight patients with prior heart transplantation who underwent CZT SPECT and
13
N-NH
3
PET dynamic scans were included in this study. CZT SPECT with
99m
Tc-sestamibi was used in the first 19 patients and
201
Tl-chloride for the remaining patients. To determine the diagnostic accuracy of angiographically defined moderate-to-severe CAV, the analysis included patients who underwent angiographic examinations within 1 year of their second scan.

Results:

There were no significant differences in the patient characteristics between the
201
Tl and
99m
Tc tracer groups. Both
201
Tl and
99m
Tc CZT SPECT-derived stress MBF and MFR values globally and in 3 coronary territories showed good correlations with
13
N-NH
3
PET. The
201
Tl and
99m
Tc cohorts did not differ significantly in the correlation coefficients of CZT SPECT versus PET for MBF and MFR, except for stress MBF (
201
Tl:0.95 versus
99m
Tc:0.80,
P
=0.03).
201
Tl and
99m
Tc CZT SPECT were satisfactory for detecting PET MFR <2.0 (
201
Tl area under the curve, 0.92 [0.71–0.99],
99m
Tc area under the curve, 0.87 [0.64–0.97]) and angiographically defined moderate-to-severe CAV, and CZT SPECT results were comparable to that of
13
N-NH
3
PET (CZT area under the curve, 0.90 [0.70–0.99], PET area under the curve, 0.86 [0.64–0.97]).

Conclusions:

This small study suggests that CZT SPECT using
201
Tl and
99m
Tc tracers showed comparable MBF and MFR, and the results correlated well with those of
13
N-NH
3
PET. Hence, CZT SPECT with
201
Tl or
99m
Tc tracers can be used to detect moderate-to-severe CAV in patients with prior heart transplantation. However, validation using larger studies is warranted.
Deep Learning Versus Neurologists: Functional Outcome Prediction in LVO Stroke Patients Undergoing Mechanical Thrombectomy
Authors: Herzog Lisa , Kook Lucas , Hamann Janne , Globas Christoph , Heldner Mirjam R. , Seiffge David , Antonenko Kateryna , Dobrocky Tomas , Panos Leonidas , Kaesmacher Johannes , Fischer Urs , Gralla Jan , Arnold Marcel , Wiest Roland , Luft Andreas R. , Sick Beate , Wegener Susanne
Published: June 2023

BACKGROUND:

Despite evolving treatments, functional recovery in patients with large vessel occlusion stroke remains variable and outcome prediction challenging. Can we improve estimation of functional outcome with interpretable deep learning models using clinical and magnetic resonance imaging data?

METHODS:

In this observational study, we collected data of 222 patients with middle cerebral artery M1 segment occlusion who received mechanical thrombectomy. In a 5-fold cross validation, we evaluated interpretable deep learning models for predicting functional outcome in terms of modified Rankin scale at 3 months using clinical variables, diffusion weighted imaging and perfusion weighted imaging, and a combination thereof. Based on 50 test patients, we compared model performances to those of 5 experienced stroke neurologists. Prediction performance for ordinal (modified Rankin scale score, 0–6) and binary (modified Rankin scale score, 0–2 versus 3–6) functional outcome was assessed using discrimination and calibration measures like area under the receiver operating characteristic curve and accuracy (percentage of correctly classified patients).

RESULTS:

In the cross validation, the model based on clinical variables and diffusion weighted imaging achieved the highest binary prediction performance (area under the receiver operating characteristic curve, 0.766 [0.727–0.803]). Performance of models using clinical variables or diffusion weighted imaging only was lower. Adding perfusion weighted imaging did not improve outcome prediction. On the test set of 50 patients, binary prediction performance between model (accuracy, 60% [55.4%–64.4%]) and neurologists (accuracy, 60% [55.8%–64.21%]) was similar when using clinical data. However, models significantly outperformed neurologists when imaging data were provided, alone or in combination with clinical variables (accuracy, 72% [67.8%–76%] versus 64% [59.8%–68.4%] with clinical and imaging data). Prediction performance of neurologists with comparable experience varied strongly.

CONCLUSIONS:

We hypothesize that early prediction of functional outcome in large vessel occlusion stroke patients may be significantly improved if neurologists are supported by interpretable deep learning models.
Intracranial Atherosclerotic Plaque Morphologic Pattern and Enhancement Change With High‐Intensity Statin Therapy
Authors: Sanchez Sebastian , Miller Jacob M. , Jones Matthew T. , Ojeda Diego J. , Samaniego Edgar A.
Published: June 2023

Background

Plaque enhancement after gadolinium contrast administration may assess plaque instability and response to medical therapy. We used high‐resolution vessel wall imaging to evaluate changes in plaque morphologic pattern and enhancement after treatment with high‐intensity statins.

Methods

Patients with a history of stroke or transient ischemic attack attributable to intracranial atherosclerotic disease underwent 7‐T high‐resolution vessel wall imaging. T1 and T1+gadolinium sequences were obtained at baseline. Follow‐up images were acquired at a minimum of 6 months after the initial scan. Low‐density lipoprotein levels were also recorded at baseline and at follow‐up, after maximal medical therapy was started. Plaque burden, degree of stenosis, and area degree of stenosis were calculated at baseline and follow‐up. Gadolinium enhancement was quantified using a 3‐dimensional pipeline for plaque analysis.

Results

Five patients were included. The mean age was 56 years, and the average time to follow‐up imaging was 17.7 months. Low‐density lipoprotein decreased from a mean of 122 to 111 mg/dL at follow‐up. Plaque burden decreased from μ=76% to 60%, area degree of stenosis decreased from μ=61% to 56%, and gadolinium uptake decreased from a mean of μ=4.11 to 3.76. Furthermore, a lower low‐density lipoprotein at follow‐up was correlated with decreased plaque burden (r=0.86), lower area degree of stenosis (r=0.8), and less gadolinium uptake (r=0.82).

Conclusions

Plaque morphologic pattern and gadolinium uptake changed at follow‐up with high‐intensity statin therapy. High‐resolution vessel wall imaging shows promise in assessing plaque response to medical therapy.
Counterfactual History: Three Worries and Replies
Authors: Zhao Helen
Published: June 2023

This article aims to shed light on what lies at the heart of skepticism towards counterfactual, alternative, or what-if history. On its face, counterfactual history gives historians and philosophers good reason to worry. First, because counterfactual pasts leave no traces, historians lack an important source of empirical warrant. Second, because rewriting historical events might unpredictably change the past, inferences about what might have happened seem only weakly supported by generalizations about what actually did happen. Third, counterfactual narratives appear especially vulnerable to wishful thinking. Ultimately, through consideration of the epistemic values that regulate the construction of counterfactual narratives, I marshal arguments against these objections and defend the legitimacy of the project. Still, I hope to show that far from being a mere ‘parlor game’, counterfactual history raises deep and provocative questions about historians’ ability to know our past, only some of which I address here.
Culture’s Impact on the Historical Sciences
Authors: Perkins T.J.
Published: June 2023

In this paper I introduce the thesis of cultural readiness about science found in the historical analysis of the Alvarez impact hypothesis of the end-Cretaceous mass extinction. Cultural readiness posits that in some scientific domains, there are scientifically apt questions, methodologies or theories that are only developed, considered, and adopted by a scientific community once some combination of empirical and cultural factors obtains within and without that domain. I demonstrate that 21st century philosophy of the historical sciences has been motivated by a commitment to legitimization and has prioritized epistemic ingenuity and has not addressed cultural readiness. I then argue that one vehicle for cultural readiness in the historical sciences is their use of narrative explanatory forms. Narratives offer an arena to blend cultural and empirical phenomena by their characteristic elicitation of familiarity and emotionality.
Narrative Explanation and Non-Epistemic Value
Authors: Turner Derek D. , AboHamad Ahmed
Published: June 2023

Explanations in the natural historical sciences often take the form of stories. This paper examines two accounts of the sources of narrative’s explanatory power: Beatty’s suggestion that narrative explanation is closely connected to historical contingency, and that narratives explain by contrasting what happened with what might have happened; and Ereshefsky and Turner’s view that narratives explain by organizing events around a central subject with a distinctive direction of historical development. In both accounts, it turns out that non-epistemic values typically play a role in the construction of narrative, and hence contribute to narrative’s explanatory force. Two case studies from historical science – the plate tectonic story of the Avalonian terrane, and the story of the evolution of trichromatic vision in (some) mammals – help to motivate and illustrate this argument.
Narrating Cultural Displacement and (Dis)Locating Beur Identity in Fouad Laroui’s De Quel Amour Blessé
Authors: Baba Nouzha
Published: June 2023

In this article, I analyse the prominent Moroccan-French author, Fouad Laroui’s novella De quel amour blessé (What Wounded Love, 1998) which narrates a story of an intercultural love affair in the diaspora, shaped in-between France and Morocco. This tragicomedy romance story, maps migrants’ cultural displacement and identity (re)construction. I look into how Maghrebian migrants’ French-born youths, known as the Beur generation, plot transcendent cultural and national routes of belonging. Through the protagonist’s case, the son of Moroccan migrants, the novella unfolds how postcolonial Maghrebian migration in France has engendered an intercultural and relational identity that belongs to different cultural subjectivities. It suggests a deconstruction of the idea that migrants’ identity are inextricably linked to a fixed culture, time and place, and instead, stresses identity as a process of becoming. Laroui’s narrative is a productive literary form of self-representation, of contesting homeland roots, (re)deconstructing identity and mapping intercultural attachments of belongings.
Speculative Cartographies
Authors: Mushaandja Nashilongweshipwe
Published: June 2023

There are far too few studies on Namibian art and artists in the diaspora. In response to this, I look at the work of Herman Mbamba, Jackson Wahengo and Shishani Vranckx. Mbamba is a visual artist based in Haugesund, Norway while musicians Wahengo and Vranckx are based in Copenhagen, Denmark and Amsterdam, The Netherlands, respectively. I offer an aesthetic reading, unpacking their work as counter-hegemonic maps, that signal the places of imagining otherwise. Wahengo and Vranckx’s songs lean towards national cultural memory while Mbamba’s abstract and figurative paintings conceal everyday realities. The concept of speculative cartography is applied, to read how these artists as African Diasporic subjects, speak to historic displacements and scatterings, while orientating themselves within national cultural memory that goes beyond ‘Namibianess’ or the African Diaspora. I argue that the speculative cartographies generate Thirdspaces that collapse binaries between settled and unsettled, imaginable and unimaginable, material and metaphysical spaces.
Paul Choart de Buzanval: A Learned French Ambassador and the Republic of Letters
Authors: De Smet Ingrid A. R.
Published: June 2023

Although he enjoys some renown as a friend of Joseph Scaliger and Isaac Casaubon, Henri iv’s ambassador to the United Provinces, Paul Choart de Buzanval (1551–1607) has rarely been studied in his own right since the 1960s. Yet Choart was a significant champion of the protestant cause, who built a network of contacts spread across Europe, from Venice over Germany to England. This article assesses, first, how Buzanval’s network grew as his career evolved during the final decades of the French Wars of Religion and their immediate aftermath. Secondly, it takes stock of Buzanval’s role as an early modern emissary abroad: it demonstrates how, over and above his diplomatic agency for Henri de Navarre/Henri iv, Buzanval also emerged as a patron and cultural intermediary with the – mostly protestant – Republic of Letters. Thus, from relatively modest beginnings, Buzanval became a notable player in a network that encompassed political as well as intellectual and merchant spheres.
The Missing Link: Modeling Readers of Multilingual Writing
Authors: Grutman Rainier
Published: June 2023

This contribution tries to fill the gap concerning the place and role of readers in multilingual studies by focusing on the ways in which multilingual texts both do and do not create multilingual readers. Three scenarios are illustrated with two examples each. So-called ‘shared multilingualism’ implies bilingual competence (and excludes monolingual readers) by juxtaposing languages with little overlap. Other texts exhibit more than one language yet construct a monolingual reader, while others still reward bilingual competence and at the same time accommodate monolingual incompetence.
Reactionary Multilingualism: Ezra Pound’s “Addendum for C”
Authors: Grønlie Espen
Published: June 2023

This article suggests a solution to the paradox that Ezra Pound both embraced literary multilingualism and endorsed ethnic segregation. The evident multilingualism of Pound’s poetry might tempt one into imagining that he was celebrating multilingualism as a societal fact. Focusing on Pound’s multilingual canto fragment “Addendum for C,” the article argues that this cannot possibly have been the case, and that a similar premise is too often taken for granted in contemporary studies of literary multilingualism.
Balkan, Creole, Other: Dislocating Contemporary Multilingualisms
Authors: Selimović Ena
Published: June 2023

Reading the language memoirs of Jhumpa Lahiri and Dubravka Ugrešić, this article investigates what it means to know or not know a language, particularly when that language is marked ‘foreign.’ The texts under analysis attend to languages that often fall under the rubric of ‘other languages’ and underexamined contact zones. Approaching the sociopolitical dominance of so-called global English and the literary marketplace of world literature, this article reveals the need to elaborate the concept of multilingualism through multiscalar reading practices that show the inter-imperial history of contemporary multilingualism.