bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure 4 from Clinical Implications and Molecular Features of Extracellular Matrix Networks in Soft Tissue Sarcomas
Authors: Pankova Valeriya , Krasny Lukas , Kerrison William , Tam Yuen B. , Chadha Madhumeeta , Burns Jessica , Wilding Christopher P. , Chen Liang , Chowdhury Avirup , Perkins Emma , Lee Alexander T.J. , Howell Louise , Guljar Nafia , Sisley Karen , Fisher Cyril , Chudasama Priya , Thway Khin , Jones Robin L. , Huang Paul H.
Published: October 2024

Identification, biological and clinical characterization of DDLPS subgroups. A, Heatmap showing the supervised clustering of 57 differentially expressed matrisome and adhesome proteins (DEPs) uniquely upregulated in each DDLPS subgroup. Black boxes indicate unique upregulated matrisome and adhesome DEPs in each of the subgroups. Bottom annotations indicate key tumor and patient characteristics. “*” Indicates that a clinical feature is significantly associated with DDLPS subgroups. B, Identities of upregulated matrisome and adhesome proteins in each DDLPS subgroup are shown on the right. Colored boxes on the right show functional pathways enriched in each DDLPS subgroup, as determined by overrepresentation analysis against the reactome pathway database. (C) Stacked bar charts showing the percentages of high and low CD3+, CD4+, and CD8+ TIL groups in each DDLPS subgroup. DDLPS cases were divided into high and low categories according to the median TILs score, separately for each stain. The χ2 test results are presented at the top of each plot. D, Significant (one-way ANOVA; FDR < 0.05) biological features obtained from ssGSEA of the MSigDB Hallmark gene sets. E, Kaplan–Meier plot of LRFS with stratification by DDLPS subgroups. Hazard ratio, 95% CI, and P-values were determined by univariate Cox regression with a two-sided Wald test.
Figure 3 from Clinical Implications and Molecular Features of Extracellular Matrix Networks in Soft Tissue Sarcomas
Authors: Pankova Valeriya , Krasny Lukas , Kerrison William , Tam Yuen B. , Chadha Madhumeeta , Burns Jessica , Wilding Christopher P. , Chen Liang , Chowdhury Avirup , Perkins Emma , Lee Alexander T.J. , Howell Louise , Guljar Nafia , Sisley Karen , Fisher Cyril , Chudasama Priya , Thway Khin , Jones Robin L. , Huang Paul H.
Published: October 2024

Generation and characterization of LMS ECM solution. A, A workflow to generate decellularized ECM LMS scaffolds from fresh frozen LMS tumors by extensive washes with detergent and generation of LMS ECM solution by incubating dried scaffolds with acidified pepsin, followed by neutralization with sodium hydroxide. Paired tumor and solidified LMS ECM solution samples were characterized by mass spectrometry. B, Venn diagram showing overlap of matrisome protein IDs consistently detected in all tumors and LMS ECM solution samples. Identities of 24 overlapping proteins are shown at the bottom. C, Box plots showing the 2D migration cell speed on plastic in GFP+ SK-UT-1 (n = 910), SK-UT-1b (n = 495), ICR-LMS-1 (n = 528), SHEF-LMS w1 (n = 996), and SHEF-LMS ws (n = 1,024) cells over 18 hours. Significance is shown following Kruskal–Wallis test with Dunn’s multiple testing correction. ****, P < 0.0001. D, Box plots showing the cell speed of GFP+ LMS cell lines on plastic or plastic precoated with LMS ECM solution. Significance is shown following Mann–Whitney U test. *, P < 0.05; **, P < 0.01; ****, P < 0.0001. E, Box plots showing the directionality indices of GFP+ LMS cell lines when grown in 2D conditions on plastic or plastic precoated with LMS ECM solution. Significance is shown following Mann–Whitney U test. *, P < 0.05; **, P < 0.01; ****, P < 0.0001. The GFP+ cells were tracked for 18 hours. Data were pooled from three independent experiments for all graphs. Boxes indicate the 25th, median, and 75th percentile, with whiskers extending from the 25th percentile − (1.5 × IQR) to the 75th percentile + (1.5 × IQR), and outliers plotted as points. F, Dot plot showing log2 normalized expression of LCP1 protein in low baseline speed cell lines (SK-UT-1, SK-UT-1B, and ICR-LMS-1), and in high baseline speed cell lines (SHEF-LMS w1 and SHEF-LMS ws). G, Kaplan–Meier plot of LRFS (left) and OS (right) with stratification by LCP1 tertiles in n = 80 LMS patients. Low LCP1 group contains patients with lower tertile (≤ −0.23 LCP1 expression), while high LCP1 group is made up of intermediate and high tertiles (> −0.23 LCP1). Hazard ratio, 95% CI, and P-values were determined by univariate Cox regression with a two-sided Wald test.
Supplementary Table 1 from Intratumoral Delivery of STING Agonist Results in Clinical Responses in Canine Glioblastoma
Authors: Boudreau C. Elizabeth , Najem Hinda , Ott Martina , Horbinski Craig , Fang Dexing , DeRay Chase M. , Levine Jonathan M. , Curran Michael A. , Heimberger Amy B.
Published: October 2024

Imaging Technique
Genome Instability Precedes Viral Integration in Human Papillomavirus–Transformed Tonsillar Keratinocytes
Authors: Chan Kimberly , Tseng Christopher , Milarachi Emily , Goldrich David , Schneper Lisa , Sheldon Kathryn , Aliaga Cesar , Alam Samina , Chatterjee Sreejata , El-Bayoumy Karam , Meyers Craig , Goldenberg David , Broach James R.
Published: October 2024

Approximately 70% of oropharyngeal squamous carcinomas (OPSCC) are associated with human papillomavirus (HPV). Although patients with HPV-positive (HPV+) tumors generally have better outcomes than those with HPV-negative tumors, a subset of HPV+ positive patients do have poor outcomes. Our previous work suggested that tumors with integrated virus exhibit significantly greater genome-wide genomic instability than those with only episomal viral genomes, and patients with HPV+ OPSCC with episomal viral genomes had better outcomes. To explore the causal relation between viral integration and genomic instability, we have examined the time course of viral integration and genetic instability in tonsillar keratinocytes transformed with HPV16. HPV-infected human tonsil keratinocyte cell lines were continuously passaged, and every fifth passage, some cells were retained for genomic analysis. Whole-genome sequencing and optical genomic mapping confirmed that virus integrated in five of six cell lines while remaining episomal in the sixth. In all lines, genome instability occurred during early passages but essentially ceased following viral integration; however, it continued to occur in later passages in the episomal line. To test tumorigenicity of the cell lines, cells were injected subcutaneously into the flanks of nude mice. A cell line with the integrated virus induced tumors following injection in the nude mouse whereas that with the episomal virus did not.

Implications: Genomic instability in HPV OPSCC tumors is not the result of viral integration but likely promotes integration. Moreover, transformants with episomal virus seem to be less tumorigenic than those with integrated virus.
Supplementary Figure S7 from IL2 Targeted to CD8+ T Cells Promotes Robust Effector T-cell Responses and Potent Antitumor Immunity
Authors: Moynihan Kelly D. , Kumar Manu P. , Sultan Hussein , Pappas Danielle C. , Park Terrence , Chin S. Michael , Bessette Paul , Lan Ruth Y. , Nguyen Henry C. , Mathewson Nathan D. , Ni Irene , Chen Wei , Lee Yonghee , Liao-Chan Sindy , Chen Jessie , Schumacher Ton N.M. , Schreiber Robert D. , Yeung Yik A. , Djuretic Ivana M.
Published: October 2024

Supplementary Figure S7: Sub-clustering of naïve-like/recently activated cluster and characterization of clonal expansion and antigen.
Supplementary Figure S6 from IL2 Targeted to CD8+ T Cells Promotes Robust Effector T-cell Responses and Potent Antitumor Immunity
Authors: Moynihan Kelly D. , Kumar Manu P. , Sultan Hussein , Pappas Danielle C. , Park Terrence , Chin S. Michael , Bessette Paul , Lan Ruth Y. , Nguyen Henry C. , Mathewson Nathan D. , Ni Irene , Chen Wei , Lee Yonghee , Liao-Chan Sindy , Chen Jessie , Schumacher Ton N.M. , Schreiber Robert D. , Yeung Yik A. , Djuretic Ivana M.
Published: October 2024

Supplementary Figure S6: Characterization of antigen-specific CD8+ T cells in MC38 tumors.
Supplementary Figure S1 from IL2 Targeted to CD8+ T Cells Promotes Robust Effector T-cell Responses and Potent Antitumor Immunity
Authors: Moynihan Kelly D. , Kumar Manu P. , Sultan Hussein , Pappas Danielle C. , Park Terrence , Chin S. Michael , Bessette Paul , Lan Ruth Y. , Nguyen Henry C. , Mathewson Nathan D. , Ni Irene , Chen Wei , Lee Yonghee , Liao-Chan Sindy , Chen Jessie , Schumacher Ton N.M. , Schreiber Robert D. , Yeung Yik A. , Djuretic Ivana M.
Published: October 2024

Supplementary Figure S1: CD8+ T cells drive anti-tumor activity but NK cells are responsible for toxicity with not-α-IL2 therapy.
Supplementary Figure S5 from USP36 SUMOylates Las1L and Promotes Its Function in Pre–Ribosomal RNA ITS2 Processing
Authors: Li Yanping , Yang Yunhan , Sears Rosalie C. , Dai Mu-Shui , Sun Xiao-Xin
Published: October 2024

Supplementary Figure S5 shows that siRNA-mediated knockdown of either Las1L or USP36 impairs the pre-rRNA ITS2 processing.
Supplementary Figure S3 from USP36 SUMOylates Las1L and Promotes Its Function in Pre–Ribosomal RNA ITS2 Processing
Authors: Li Yanping , Yang Yunhan , Sears Rosalie C. , Dai Mu-Shui , Sun Xiao-Xin
Published: October 2024

Supplementary Figure S3 Shows that Las1L SUMOylation at K565 affects its nucleoplasmic translocation.
Supplementary Figure S2 from USP36 SUMOylates Las1L and Promotes Its Function in Pre–Ribosomal RNA ITS2 Processing
Authors: Li Yanping , Yang Yunhan , Sears Rosalie C. , Dai Mu-Shui , Sun Xiao-Xin
Published: October 2024

Supplementary Figure S2 shows the SUMOylation of full-length Las1L and its N-terminal deletion mutant (aa 189–613) and that K565 is the main SUMOylation site.
Supplementary Figure S1 from USP36 SUMOylates Las1L and Promotes Its Function in Pre–Ribosomal RNA ITS2 Processing
Authors: Li Yanping , Yang Yunhan , Sears Rosalie C. , Dai Mu-Shui , Sun Xiao-Xin
Published: October 2024

Supplementary Figure S1 shows the cellular localization of USP36 and its deletion mutants by IF.
Figure 7 from USP36 SUMOylates Las1L and Promotes Its Function in Pre–Ribosomal RNA ITS2 Processing
Authors: Li Yanping , Yang Yunhan , Sears Rosalie C. , Dai Mu-Shui , Sun Xiao-Xin
Published: October 2024

Las1L SUMOylation at K565 is critical for its function in rRNA ITS2 processing. The HEK293 (A and B) and HeLa (C and D) cells transfected with scr or Las1L siRNA together with siRNA-resistant WT Flag-Las1L or its K565R mutant were assayed for rRNA ITS2 processing by Northern blot analysis using the ITS2 probe. The 32S rRNA precursor and the relative ratios of 32S to 28S rRNA normalized to the scr control are indicated in the top panels. Ethidium bromide (EB) staining of the RNA agarose gel is shown in the bottom panels (A and C). One representative experiment from three independent experiments is shown. The expression of the endogenous Las1L and exogenous Flag-Las1L is shown by IB (B and D).
Figure 6 from USP36 SUMOylates Las1L and Promotes Its Function in Pre–Ribosomal RNA ITS2 Processing
Authors: Li Yanping , Yang Yunhan , Sears Rosalie C. , Dai Mu-Shui , Sun Xiao-Xin
Published: October 2024

The Las1L–Nol9 complex and USP36 play a role in rRNA ITS2 processing. The HEK293 and HeLa cells transfected with scr, Las1L, Nol9 siRNA (A and B), or USP36 siRNA (C and D) were assayed for rRNA processing by Northern blot analysis using probe hybridizing to the ITS2 (A and C). The 47S pre-rRNA, 32S rRNA, 12S rRNA, and the relative ratios of 32S to 28S rRNA normalized to the scr control are shown in the top panels. Ethidium bromide (EB) staining of the RNA gels to indicate 28S and 18S rRNAs is shown in the bottom panels (A and C). The protein expression is shown by IB (B and D).
Figure 4 from USP36 SUMOylates Las1L and Promotes Its Function in Pre–Ribosomal RNA ITS2 Processing
Authors: Li Yanping , Yang Yunhan , Sears Rosalie C. , Dai Mu-Shui , Sun Xiao-Xin
Published: October 2024

USP36 SUMOylates Las1L. A, Las1L is SUMOylated in cells. H1299 cells transfected with Flag-Las1L in the absence or presence of His-SUMO1 or His-SUMO2 were subjected to Ni2+-NTA PD under denaturing conditions, followed by IB with anti-Flag, anti-SUMO1, and anti-SUMO2/3 antibodies. B, USP36 promotes Las1L SUMOylation. H1299 cells transfected with the indicated plasmids were subjected to Ni2+-NTA PD, followed by IB to detect Las1L SUMOylation. The SUMOylated Las1L and total SUMOylated proteins are indicated. The protein expression is shown in the bottom panels. C, Knockdown of endogenous USP36 reduces Las1L SUMOylation. H1299 cells transfected with the indicated plasmids together with scr or USP36 siRNA were subjected to Ni2+-NTA PD, followed by IB to detect Las1L SUMOylation. The protein expression is shown in the bottom panels. D and E, Las1L is SUMOylated at K565. H1299 cells transfected with WT Las1L or the indicated lysine mutant plasmids were subjected to Ni2+-NTA beads PD under denaturing conditions, followed by IB. The SUMOylated Las1L and total SUMOylated proteins are indicated. The protein expression is shown in the bottom panels. The relative ratio of SUMOylated Las1L to native Las1L normalized to WT Las1L from the four individual experiments are shown in E.
Supplementary Data from Combinatorial Natural Killer Cell–based Immunotherapy Approaches Selectively Target Chordoma Cancer Stem Cells
Authors: Hoke Austin T.K. , Padget Michelle R. , Fabian Kellsye P. , Nandal Anjali , Gallia Gary L. , Bilusic Marijo , Soon-Shiong Patrick , Hodge James W. , London Nyall R.
Published: October 2024

Supplementary Data
TABLE 1 from In Silico Epitope Prediction Analyses Highlight the Potential for Distracting Antigen Immunodominance with Allogeneic Cancer Vaccines
Authors: James C. Alston , Ronning Peter , Cullinan Darren , Cotto Kelsy C. , Barnell Erica K. , Campbell Katie M. , Skidmore Zachary L. , Sanford Dominic E. , Goedegebuure S. Peter , Gillanders William E. , Griffith Obi L. , Hawkins William G. , Griffith Malachi
Published: October 2024

Summary of phase III clinical trials involving allogeneic cancer vaccines.
FIGURE 5 from In Silico Epitope Prediction Analyses Highlight the Potential for Distracting Antigen Immunodominance with Allogeneic Cancer Vaccines
Authors: James C. Alston , Ronning Peter , Cullinan Darren , Cotto Kelsy C. , Barnell Erica K. , Campbell Katie M. , Skidmore Zachary L. , Sanford Dominic E. , Goedegebuure S. Peter , Gillanders William E. , Griffith Obi L. , Hawkins William G. , Griffith Malachi
Published: October 2024

Genome-wide germline variant and alloantigen analysis. A, Alloantigen analysis in a single simulation of a melanoma clinical trial. Nonspecific alloantigen presentation provided by allogeneic vaccines are quantified for each of 30 patients. Unique protein altering variants (teal) are shown along with those predicted to be strong binding (IC50 < 500 nm) by cell based (tan) and lysate-based (green) analysis. B, Alloantigen analysis for five common cancer types, lysate and cell-based. The counts of predicted alloantigens corresponding to 10 simulated vaccine trials for five cancer types (300 simulated patients per cancer type) are depicted as violin plots for both a lysate-based (top) and cell-based (bottom) analysis.
FIGURE 4 from Combinatorial Natural Killer Cell–based Immunotherapy Approaches Selectively Target Chordoma Cancer Stem Cells
Authors: Hoke Austin T.K. , Padget Michelle R. , Fabian Kellsye P. , Nandal Anjali , Gallia Gary L. , Bilusic Marijo , Soon-Shiong Patrick , Hodge James W. , London Nyall R.
Published: October 2024

Doublet treatment of chordoma cells with N-601 (anti-PD-L1) and cetuximab (anti-EGFR) further enhances sensitivity to lysis by N-803 (IL15 superagonist)-activated NK cells. Two chordoma cell lines (UM-Chor1, JHC7) were used as targets for healthy donor NK cells in 111In-release killing assays. Chordoma cells were co-incubated with isotype control antibody, N-601, and/or cetuximab and NK cells were treated with N-803 where indicated. All E:T ratios are 10:1 to prevent excess tumor cell lysis and allow for the assessment of incremental enhancement by triple combination therapy. Statistical analyses were done by one-way ANOVA with Tukey's multiple comparisons test. *P d 0.05, **P d 0.01, ***P d 0.001, ****P d 0.0001. Results shown are the means ± SEM of technical triplicate measurements and are representative of three independent experiments.
FIGURE 3 from Combinatorial Natural Killer Cell–based Immunotherapy Approaches Selectively Target Chordoma Cancer Stem Cells
Authors: Hoke Austin T.K. , Padget Michelle R. , Fabian Kellsye P. , Nandal Anjali , Gallia Gary L. , Bilusic Marijo , Soon-Shiong Patrick , Hodge James W. , London Nyall R.
Published: October 2024

Chordoma cell susceptibility to killing by healthy donor NK cells is enhanced by cetuximab (anti-EGFR) and combination treatment with N-803 (IL15 superagonist) and cetuximab. Six chordoma cell lines (UM-Chor1, MUG-CC1, UM-Chor5, JHC7, U-CH1, U-CH2) were used as targets for healthy donor NK cells in 111In-release killing assays. A, Cetuximab-mediated ADCC assays were performed by co-incubating chordoma cells with N-601 or isotype control antibody. NK cells were treated with anti-CD-16 antibody where indicated. B, Combination treatment assays were performed by co-incubating chordoma cells with cetuximab or isotype control antibody and treating NK cells with N-803 and/or anti-CD-16 antibody where indicated. All E:T ratios are 20:1. Statistical analyses were done by one-way ANOVA with Tukey's multiple comparisons test. *P d 0.05, **P d 0.01, ***P d 0.001, ****P d 0.0001. Results shown are the means ± SEM of technical triplicate measurements and are representative of three independent experiments.
FIGURE 2 from Combinatorial Natural Killer Cell–based Immunotherapy Approaches Selectively Target Chordoma Cancer Stem Cells
Authors: Hoke Austin T.K. , Padget Michelle R. , Fabian Kellsye P. , Nandal Anjali , Gallia Gary L. , Bilusic Marijo , Soon-Shiong Patrick , Hodge James W. , London Nyall R.
Published: October 2024

Chordoma cell susceptibility to lysis by healthy donor NK cells is enhanced by N-601 (anti-PD-L1), N-803 (IL15 superagonist), and combination treatment with N-601 and N-803. Six chordoma cell lines (UM-Chor1, MUG-CC1, UM-Chor5, JHC7, U-CH1, U-CH2) were used as targets for healthy donor NK cells in 111In-release killing assays. A, N-601-mediated ADCC assays were performed by co-incubating chordoma cells with N-601 or isotype control antibody. NK cells were treated with anti-CD-16 antibody where indicated. B, Combination treatment assays were performed by co-incubating chordoma cells with N-601 or isotype control antibody and treating NK cells with N-803 and/or anti-CD-16 antibody where indicated. All E:T ratios are 20:1. Statistical analyses were done by one-way ANOVA with Tukey's multiple comparisons test. *P d 0.05, **P d 0.01, ***P d 0.001, ****P d 0.0001. Results shown are the means ± SEM of technical triplicate measurements and are representative of three independent experiments.
FIGURE 1 from Combinatorial Natural Killer Cell–based Immunotherapy Approaches Selectively Target Chordoma Cancer Stem Cells
Authors: Hoke Austin T.K. , Padget Michelle R. , Fabian Kellsye P. , Nandal Anjali , Gallia Gary L. , Bilusic Marijo , Soon-Shiong Patrick , Hodge James W. , London Nyall R.
Published: October 2024

Anatomically distinct chordoma cell lines are susceptible to lysis by healthy donor natural killer (NK) cells. Chordoma cell killing by 25 healthy NK cell donors as determined by 111In-release killing assays. Each data point represents a distinct healthy NK cell donor. All E:T ratios are 20:1. Statistical analyses were done by Student's t-test. *P d 0.05, **P d 0.01, ***P d 0.001, ****P d 0.0001. Results shown are the means ± SEM of at least five independent experiments.
FIGURE 2 from In Silico Epitope Prediction Analyses Highlight the Potential for Distracting Antigen Immunodominance with Allogeneic Cancer Vaccines
Authors: James C. Alston , Ronning Peter , Cullinan Darren , Cotto Kelsy C. , Barnell Erica K. , Campbell Katie M. , Skidmore Zachary L. , Sanford Dominic E. , Goedegebuure S. Peter , Gillanders William E. , Griffith Obi L. , Hawkins William G. , Griffith Malachi
Published: October 2024

TAA expression analysis. A, TAA expression in a single simulation of a pancreatic adenocarcinoma clinical trial. Tumor associated antigen counts (MUC1 and Mesothelin for PAAD) are summarized for an example trial simulation in pancreatic adenocarcinoma. TAAs were assessed for each patient after taking into account the MHC alleles for either patient only (lysate-based analysis) or patient and vaccine (cell-based analysis), requiring evidence for both presentation of TAA peptide and robust expression of the TAA gene (Methods). B, TAA expression in each of five cancer types. For each cancer type, select established TAA genes were considered (Gp100, Ny-ESO-1 and MART-1 for SKCM; VEGFR1 and Ny-ESO-1 for LUAD; VEGFR1 and Ny-ESO-1 for LUSC; PSA and PAP for PRAD). Counts of expressed TAAs across 300 patients for each tumor type are shown as violin plots with individual points representing the count for each simulated patient overlaid.
Figure S4 from A Database Tool Integrating Genomic and Pharmacologic Data from Adrenocortical Carcinoma Cell Lines, PDX, and Patient Samples
Authors: Arakawa Yasuhiro , Elloumi Fathi , Varma Sudhir , Khandagale Prashant , Jo Ukhyun , Kumar Suresh , Roper Nitin , Reinhold William C. , Robey Robert W. , Takebe Naoko , Gottesman Michael M. , Thomas Craig J. , Boeva Valentina , Berruti Alfredo , Abate Andrea , Tamburello Mariangela , Sigala Sandra , Hantel Constanze , Weigand Isabel , Wierman Margaret E. , Kiseljak-Vassiliades Katja , Del Rivero Jaydira , Pommier Yves
Published: October 2024

Supplement Figure 4
Figure 8 from A Database Tool Integrating Genomic and Pharmacologic Data from Adrenocortical Carcinoma Cell Lines, PDX, and Patient Samples
Authors: Arakawa Yasuhiro , Elloumi Fathi , Varma Sudhir , Khandagale Prashant , Jo Ukhyun , Kumar Suresh , Roper Nitin , Reinhold William C. , Robey Robert W. , Takebe Naoko , Gottesman Michael M. , Thomas Craig J. , Boeva Valentina , Berruti Alfredo , Abate Andrea , Tamburello Mariangela , Sigala Sandra , Hantel Constanze , Weigand Isabel , Wierman Margaret E. , Kiseljak-Vassiliades Katja , Del Rivero Jaydira , Pommier Yves
Published: October 2024

The CU-ACC1 cell line is sensitive to temozolomide as it lacks MGMT and is MMR proficient, whereas CU-ACC2 cells are resistant to temozolomide because of MMR deficiency. A, CU-ACC1 and CU-ACC2 do not express MGMT transcripts. Univariate scatterplot of MGMT transcriptional expression levels vs. MGMT gene promoter methylation levels in the ACC cell line dataset. B, MGMT protein expression levels in CU-ACC1, CU-ACC2, NCI-H295R, and SW-13. Proteins were extracted from each cell line, and MGMT expression was assessed by Western blotting. C, The CU-ACC2 cell line is defective in MMR due to lack of expression of the MSH2 gene. Univariate scatter plot of MHS2 transcript levels vs. MSH2 gene copy number in the ACC cell lines data set. D, Dose–response curves of temozolomide in CU-ACC1, CU-ACC2, NCI-H295R, and SW-13. Cell viability was assessed after 72 hours under the indicated drug concentrations by CellTiter-Glo assay.
Figure 5 from A Database Tool Integrating Genomic and Pharmacologic Data from Adrenocortical Carcinoma Cell Lines, PDX, and Patient Samples
Authors: Arakawa Yasuhiro , Elloumi Fathi , Varma Sudhir , Khandagale Prashant , Jo Ukhyun , Kumar Suresh , Roper Nitin , Reinhold William C. , Robey Robert W. , Takebe Naoko , Gottesman Michael M. , Thomas Craig J. , Boeva Valentina , Berruti Alfredo , Abate Andrea , Tamburello Mariangela , Sigala Sandra , Hantel Constanze , Weigand Isabel , Wierman Margaret E. , Kiseljak-Vassiliades Katja , Del Rivero Jaydira , Pommier Yves
Published: October 2024

Several ACC cell lines and surgical samples do not express TERT. A, Univariate scatterplot of TERT transcriptional expression levels vs. ATRX transcriptional expression levels in the ACC cell line and surgical sample data set. B, Alternative lengthening of telomeres (ALT)-associated PML body formation. Representative confocal micrograph images of ALT cell line (U2OS) and ACC cell lines. Cells were fixed and immunofluorescently labeled with Abs against TERF2 and PML; TERF2 was stained green, PML red, and nuclei DAPI blue. C, DAXX and ATRX mutations in Colorado, Zurich, and Wurzburg data sets. Mutation scores in each dataset were collected and plotted; MUC-1 and CU-ACC2 have ATRX mutations, and JIL-2266 has DXAA mutation.
Data from USP36 SUMOylates Las1L and Promotes Its Function in Pre–Ribosomal RNA ITS2 Processing
Authors: Li Yanping , Yang Yunhan , Sears Rosalie C. , Dai Mu-Shui , Sun Xiao-Xin
Published: October 2024

Abstract
Ribosome biogenesis is a highly regulated cellular process requiring a large cohort of accessory factors to ensure the accurate production of ribosomes. Dysregulation of ribosome biogenesis is associated with the development of various human diseases, including cancer. The Las1L–Nol9 endonuclease–kinase complex is essential for the cleavage of the rRNA internal transcribed spacer 2 (ITS2), the phosphorylation of the 5′-hydroxyl end of the resulting precursor, and, thus, the maturation of the 60S ribosome. However, how the Las1L–Nol9 complex is regulated in cells is unclear. In this study, we report that the nucleolar ubiquitin-specific protease USP36 is a novel regulator of the Las1L–Nol9 complex. USP36 interacts with both Las1L and Nol9 and regulates their stability via deubiquitination. Intriguingly, USP36 also mediates the SUMOylation of Las1L, mainly at lysine (K) 565. Mutating K565 to arginine (R) does not affect the levels of Las1L and the formation of the Las1L–Nol9 complex, but abolishes its function in ITS2 processing, as unlike wild-type Las1L, the K565R mutant failed to rescue the defects in the ITS2 processing induced by the knockdown of endogenous Las1L. These results suggest that USP36-mediated Las1L SUMOylation is critical for ITS2 processing and that USP36 plays a critical role in ribosome biogenesis by regulating the Las1L–Nol9 complex.
Significance:
This study identifies USP36 as a deubiquitinating and small ubiquitin-like modifier ligase dual-function enzyme to mediate Las1L deubiquitination and SUMOylation. Las1L SUMOylation at K565 plays a critical role in pre-rRNA ITS2 processing. Thus, our study reveals a novel downstream pathway for USP36-regulated ribosome biogenesis.
Effectiveness of a Sugar Consumption Prevention Program in the First Year of Life on the Occurrence of Early Childhood Caries: A Multicentric Randomized Trial in Brazil
Authors: Feldens Carlos Alberto , de Barros Coelho Elisa Maria Rosa , Vítolo Márcia Regina , Rogrigues Priscila Humbert , Kramer Paulo Floriani , Peres Karen Glazer
Published: October 2024

Introduction: This study aimed to investigate the effectiveness of a nutritional counseling program for mothers of newborns to prevent sugar consumption in the first year of life on the occurrence of early childhood caries (ECC). Methods: A multicentric randomized clinical trial (ClinicalTrials.gov – NCT03841123) was conducted in three state capitals of Brazil (n = 516). Mothers were randomly assigned to the intervention group (IG) or control group (CG) after delivery. The IG received face-to-face nutritional counseling based on UNICEF dietary guidelines after delivery, followed by monthly phone calls. The CG received standard counseling. Dietary intake was measured through structured questionnaires and 24-h recalls at 6 and 12 months. Dental clinical examination for ECC diagnosis was performed by calibrated dentists after the children completed the first year of life. Results: The prevalence of ECC was 17.4% in the overall sample (49/290). The number of affected teeth ranged from 0 to 6 (mean 0.43). The IG had a 2.4 times probability of not consuming sugar in the first 6 months of life (RR 2.44; 95% CI: 1.18–5.00) and a significantly lower mean number of sweet items consumed at 12 months (p = 0.016). However, no significant differences between groups were found with regard to the occurrence of ECC (RR 1.33; 95% CI: 0.79–2.25) or the number of teeth affected by caries (p = 0.273). Conclusion: The intervention to prevent and reduce sugar intake in the first year of life was not effective at reducing the occurrence of ECC or the number of teeth with carious lesions.
Chronic Hepatitis B Costs and Healthcare Resource Utilization in a Japanese Patient Population: A Retrospective Cross-Sectional Analysis
Authors: Ju Shinyoung , Katsumata Masayuki , Mizukami Akiko , Abersone Ilze , Gielen Vera
Published: October 2024

Introduction: Data on the economic burden of chronic hepatitis B infection in Japan are lacking. This study investigated healthcare resource utilization and costs of chronic hepatitis B infection and liver complications in Japan. Methods: This non-interventional study used the Medical Data Vision database. For the first analysis, a population with prevalent chronic hepatitis B infection and absence of liver complications was identified and further stratified by nucleos(t)ide analog treatment history. In the second analysis, patients with prevalent chronic hepatitis B infection and incident liver complications were identified. Patients were followed for 1 year in the first analysis and 2 years in the second analysis. Numbers of all-cause outpatient, inpatient, emergency hospitalizations, medication use, and associated costs per person-year were described across patients without/with nucleos(t)ide analog treatment and in those without/with liver complications. Results: For patients with chronic hepatitis B infection, 75,967 had no liver complications while 17,678 patients had liver complications. All-cause outpatient visits were the largest contributor to healthcare resource utilization and costs, for patients without and with liver complications, and were numerically higher for patients on nucleos(t)ide analog than not. Patients with liver complications had numerically higher all-cause healthcare resource utilization and total costs than patients without complications. Conclusions: Japan has a high economic burden of chronic hepatitis B infection, particularly in patients with liver complications. Optimizing treatment to prevent complications may reduce this burden.
Diagnostic Accuracy of Tryptase Levels for Pediatric Anaphylaxis: A Case-Control Study
Authors: Khalaf Roy , Prosty Connor , McCusker Christine , Bretholz Adam , Kaouache Mohammed , Clarke Ann E. , Ben-Shoshan Moshe
Published: October 2024

Introduction: Anaphylaxis is a severe allergic reaction which can be difficult to diagnose. Two strategies evaluating changes in tryptase levels were proposed for diagnosing anaphylaxis. Strategy 1 established a threshold of tryptase levels during reaction exceeding 2 ng/mL + 1.2* (baseline tryptase levels) as a rule for detecting anaphylaxis, while strategy 2 established the ratio of tryptase levels during reaction versus baseline tryptase exceeding a threshold of 1.685. We aimed to compare the diagnostic test accuracy of the two strategies in pediatric anaphylaxis. Methods: We conducted a case-control study. Cases consisted of 89 patients with anaphylaxis who had reaction tryptase and subsequent baseline tryptase measured. Controls consisted of 25 patients with chronic urticaria who had two tryptase measurements. Sensitivity and specificity for each of the strategies were computed and compared using McNemar test. The area under the curve (AUC) between the two strategies was compared using the DeLong test. Results: The sensitivity and specificity for strategy 1 was 53.3% and 95.0%, respectively. For strategy 2, the sensitivity and specificity was 54.4% and 85.0%, respectively. There was no significant difference between both strategies’ sensitivity and specificity. The Delong test determined that the AUC was significantly (p < 0.05) higher for strategy 1 (0.69) than strategy 2 (0.64). Conclusion: The Delong test determined that strategy 1 was slightly better in validating anaphylaxis diagnosis than strategy 2. However, both strategies demonstrated a low sensitivity <55%.
Challenges in Beta Cell Replacement for Type 1 Diabetes
Authors: Lemos Joana R.N. , Skyler Jay S.
Published: October 2024

Background: Type 1 diabetes (T1D), a disease characterized by immune-mediated destruction of beta-cells, presents a significant global health challenge. Achieving therapeutic goals such as prevention of immune destruction, preservation of beta-cell mass, and automated insulin delivery remains complex due to the disease’s heterogeneity. Summary: This review explores the advancements and challenges in beta-cell replacement therapies, including pancreas and islet cell transplantation, stem cell-derived β-cell generation, and biotechnological innovations. Pancreas transplantation, especially simultaneous pancreas and kidney transplantation, has evolved significantly, offering insulin independence and improved quality of life despite surgical and immunological complications. Allogeneic islet transplantation, though less invasive, faces challenges such as donor scarcity, immunosuppressive therapy, and variable long-term success. Innovations in stem cell therapy, particularly using human embryonic stem cells and induced pluripotent stem cells, promise an unlimited source of β-cells. However, translating these advances into clinical applications involves overcoming technical, biological, and ethical hurdles. Strategies such as immunomodulation, encapsulation, and genetic engineering are critical to enhancing the viability and integration of transplanted cells. Key Messages: This review provides a comprehensive overview of the scientific intricacies and potential of β-cell replacement therapies, emphasizing the need for continued research to address the remaining challenges and improve diabetes care outcomes.
Efficacy and Safety of Upadacitinib versus Dupilumab Treatment for Moderate-to-Severe Atopic Dermatitis in Four Body Regions: Analysis from the Heads Up Study
Authors: Thyssen Jacob P. , Rosmarin David , Costanzo Antonio , Warren Richard , Chu Chia-Yu , Chovatiya Raj , Ladizinski Barry , Hu Xiaofei , Liu Yingyi , Calimlim Brian , Nduaka Chudi , Vigna Namita , Armstrong April
Published: October 2024

Introduction: Upadacitinib has demonstrated high and rapid rates of efficacy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) as assessed by the Eczema Area and Severity Index (EASI). This post hoc analysis assessed the EASI response in four anatomical regions for patients with moderate-to-severe AD treated with upadacitinib compared to dupilumab over 24 weeks. Methods: Data from patients randomized 1:1 to receive upadacitinib 30 mg extended-release tablet orally once daily or dupilumab 300 mg by subcutaneous injection every 2 weeks after a loading dose of 600 mg in the Heads Up study were analyzed for achievement of ≥75%, ≥90%, or 100% reduction of EASI in four body regions: (1) head and neck, (2) trunk (including genitals), (3) upper limbs, and (4) lower limbs (including buttocks) at each study visit through week 24. Patient response data from the Head and Neck Patient Global Impression of Severity (HN-PGIS) were also analyzed at each study visit for comparison of upadacitinib to dupilumab. Results: Greater proportions of patients treated with upadacitinib versus dupilumab achieved skin clearance rates of ≥75% (EASI 75) at week 1 and higher clearance rates of ≥90% (EASI 90) or 100% (EASI 100) by week 4 or earlier in all four body regions. This difference was maintained at each visit through week 24 for both EASI 90 and EASI 100. Patient responses on the HN-PGIS indicated that a greater proportion of patients (nominal p value <0.05) treated with upadacitinib compared to dupilumab reported that AD symptoms in the head and neck region were absent or minimal as early as week 1. Conclusion: Compared to dupilumab, upadacitinib treatment provided higher rates of rapid, sustained efficacy for the head and neck, trunk, upper limbs, and lower limbs for the treatment of moderate-to-severe AD as measured by the EASI and supported by patient responses.
O discurso financeiro em peças publicitárias de bancos brasileiros na era moderna
Authors: Spinelli Egle Müller , Martinez Cássio
Published: October 2024

Este artigo tem como objetivo observar práticas de consumo com base no discurso de peças publicitária de instituições financeiras. Para tanto, conceituamos as relações de consumo com a modernidade para dar bases teóricas na condução de uma análise de discurso francesa a partir de três peças publicitárias de bancos nacionais veiculadas entre os anos de 1950 e 1970: Banco Cruzeiro do Sul, Casa Bancária Monero e União de Bancos Brasileiros. Nesse sentido, busca-se averiguar a impregnação do ethos de modernidade instituído pelo discurso publicitário dos bancos nos consumidores, com o intuito de compreender a promoção do consumo de produtos financeiros e o papel dos bancos na ampliação do capitalismo financeirizado na vida cotidiana.
Gerados por IA: modelos virtuais e suas implicações de uso na moda
Authors: Araujo Leila , Peruzzo André
Published: October 2024

The popularization of the use of artificial intelligence processes and systems has significantly grown among fashion companies and brands. In this context, this study examines the recent phenomenon of virtual models generated by artificial intelligence, exploring their definitions, ethical implications, and their current presence in the e-commerce of brands. For this, academic discussions, trend reports, and market data are reviewed in conjunction with a case study of the partnership between Levi Strauss & Co. and the Lalaland studio. Results indicate opportunities in the use of virtual models – such as a possible promotion of sustainability and resource optimization for fashion brands – and significant challenges, including issues related to algorithmic biases and diversity and inclusion in model representation.
A concepção de Duhem de História da Ciência como história intelectual - teses historiográficas e metodologia da continuidade e da convergência
Authors: Chiappin José Raymundo Novaes , Silva Jojomar Lucena da
Published: October 2024

O objetivo deste artigo é apresentar a concepção de história da ciência de Duhem como história intelectual e defender a tese de que se trata de uma concepção continuísta e teleológica, com a função de prover à concepção de ciência uma dinâmica que garanta o valor de conhecimento. De maneira subsidiaria, far-se-á a introdução de uma segunda concepção de história, formal, mais restritiva por ser fruto exclusivo da lógica e da base empírica da ciência, e mostrar que é sobre esse cenário onde a história da ciência se apresenta, primeiramente, como contínua e teleológica. Esse artigo é o desenvolvimento de outro publicado alhures. Defendemos, agora, que cada uma das concepções de história, formal e intelectual, tem naturezas e funções próprias que revelam recursos diferentes das partes metodológicas da concepção da teoria da ciência.
An interval prediction approach for quantifying the thermal error uncertainty of ball screw system
Authors: Qin Qingzhen , Li Liang , Zhao Guolong , Chen Ni
Published: October 2024

The ball screw system is one of the most core components of CNC machine tool, and its thermal positioning error directly affects the machining accuracy of parts. Establishing a data-based thermal error model is currently a popular method to predict this thermal error. Uncertain disturbances are unavoidable in reality. However, most of the existing thermal error models are deterministic, which cannot consider the uncertainty and generally can only provide the predictive value. To quantify the uncertainty of thermal error from the ball screw system, this paper proposes an interval prediction method, in which gated recurrent unit (GRU) neural network is embedded into the model and prediction interval (PI) evaluation indexes are used to determine the model parameters. Both the temporal and spatial characteristics of thermal error in the ball screw system are taken into account by the proposed method. The experimental data has verified that the proposed method can effectively generate PIs for the thermal error of ball screw system.
The application of explainable artificial intelligence (XAI) in electronic health record research: A scoping review
Authors: Caterson Jessica , Lewin Alexandra , Williamson Elizabeth
Published: October 2024

Machine Learning (ML) and Deep Learning (DL) models show potential in surpassing traditional methods including generalised linear models for healthcare predictions, particularly with large, complex datasets. However, low interpretability hinders practical implementation. To address this, Explainable Artificial Intelligence (XAI) methods are proposed, but a comprehensive evaluation of their effectiveness is currently limited. The aim of this scoping review is to critically appraise the application of XAI methods in ML/DL models using Electronic Health Record (EHR) data. In accordance with PRISMA scoping review guidelines, the study searched PUBMED and OVID/MEDLINE (including EMBASE) for publications related to tabular EHR data that employed ML/DL models with XAI. Out of 3220 identified publications, 76 were included. The selected publications published between February 2017 and June 2023, demonstrated an exponential increase over time. Extreme Gradient Boosting and Random Forest models were the most frequently used ML/DL methods, with 51 and 50 publications, respectively. Among XAI methods, Shapley Additive Explanations (SHAP) was predominant in 63 out of 76 publications, followed by partial dependence plots (PDPs) in 11 publications, and Locally Interpretable Model-Agnostic Explanations (LIME) in 8 publications. Despite the growing adoption of XAI methods, their applications varied widely and lacked critical evaluation. This review identifies the increasing use of XAI in tabular EHR research and highlights a deficiency in the reporting of methods and a lack of critical appraisal of validity and robustness. The study emphasises the need for further evaluation of XAI methods and underscores the importance of cautious implementation and interpretation in healthcare settings.
Composition of the Earth and implications for geodynamics
Authors: McDonough William F.
Published: October 2024

The composition of the bulk silicate Earth (BSE) is the product of planetary accretion, core differentiation and Moon formation. By establishing the composition of the BSE, one can determine the composition of the bulk Earth and by subtraction, calculate the core’s composition. The BSE represents the bulk Earth minus the core, which in today’s terms equals the modern mantle, the continental crust, and the hydrosphere-atmosphere systems. The modern mantle can be framed in terms of two compositionally distinct components, an enriched and a depleted mantle, with the latter as the MORB (mid-ocean ridge basalt) source and the former as the OIB (ocean island basalt) source.
Bank vole genomics links determinate and indeterminate growth of teeth
Authors: Calamari Zachary T. , Song Andrew , Cohen Emily , Akter Muspika , Das Roy Rishi , Hallikas Outi , Christensen Mona M. , Li Pengyang , Marangoni Pauline , Jernvall Jukka , Klein Ophir D.
Published: October 2024

Background

Continuously growing teeth are an important innovation in mammalian evolution, yet genetic regulation of continuous growth by stem cells remains incompletely understood. Dental stem cells responsible for tooth crown growth are lost at the onset of tooth root formation. Genetic signaling that initiates this loss is difficult to study with the ever-growing incisor and rooted molars of mice, the most common mammalian dental model species, because signals for root formation overlap with signals that pattern tooth size and shape (i.e., cusp patterns). Bank and prairie voles (Cricetidae, Rodentia, Glires) have evolved rooted and unrooted molars while retaining similar size and shape, providing alternative models for studying roots.

Results

We assembled ade novogenome ofMyodes glareolus, a vole with high-crowned, rooted molars, and performed genomic and transcriptomic analyses in a broad phylogenetic context of Glires (rodents and lagomorphs) to assess differential selection and evolution in tooth forming genes. Bulk transcriptomics comparisons of embryonic molar development between bank voles and mice demonstrated overall conservation of gene expression levels, with species-specific differences corresponding to the accelerated and more extensive patterning of the vole molar. We leverage convergent evolution of unrooted molars across the clade to examine changes that may underlie the evolution of unrooted molars. We identified 15 dental genes with changing synteny relationships and six dental genes undergoing positive selection across Glires, two of which were undergoing positive selection in species with unrooted molars,DsppandAqp1. Decreased expression of both genes in prairie voles with unrooted molars compared to bank voles supports the presence of positive selection and may underlie differences in root formation.

Conclusions

Our results support ongoing evolution of dental genes across Glires and identify candidate genes for mechanistic studies of root formation. Comparative research using the bank vole as a model species can reveal the complex evolutionary background of convergent evolution for ever-growing molars.
Analgesic regimens administered to older adults receiving skilled nursing facility care following hip fracture: a proof-of-concept federated analysis
Authors: Zullo Andrew R. , Riester Melissa R. , Hayes Kaleen N. , Zhang Yuan , Berry Sarah D. , Belanger Emmanuelle , Cupp Meghan A. , Beaudoin Francesca L.
Published: October 2024

Background

Although a majority of patients in the U.S. receive post-acute care in skilled nursing facilities (SNFs) following hip fracture, large-sample observational studies of analgesic prescribing and use in SNFs have not been possible due to limitations in available data sources. We conducted a proof-of-concept federated analysis of electronic health records (EHRs) from 11 SNF chains to describe analgesic use during hip fracture post-acute care.

Methods

We included residents with a diagnosis of hip fracture between January 1, 2018 and June 30, 2021 who had at least one administration of an analgesic. Use of analgesics was ascertained from EHR medication orders and medication administration records. We quantified the proportion of residents receiving analgesic regimens based on the medications that were administered up to 100 days after hip fracture diagnosis. Plots visualizing trends in analgesic use were stratified by multiple resident characteristics including age and Alzheimer’s Disease and Related Dementias (ADRD) diagnosis.

Results

The study included 23,706 residents (mean age 80.5 years, 68.6% female, 87.7% White). Most (~ 60%) residents received opioids + APAP. Monotherapy with APAP or opioids was also common. The most prevalent regimens were oxycodone + APAP (20.1%), hydrocodone + APAP (15.8%), APAP only (15.1%), tramadol + APAP (10.4%), and oxycodone only (4.3%). During the study period, use of APAP-only increased, opioids-only decreased, and opioids + APAP remained stable. Use of APAP-only appeared to be more prevalent among individuals aged > 75 years (versus ≤ 75 years) and those with ADRD (versus without).

Conclusions

We successfully leveraged federated SNF EHR data to describe analgesic use among residents receiving hip fracture post-acute care.