bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi‐purpose Japanese phase I study in the global development of vupanorsen: Randomized, placebo‐controlled, single‐ascending dose study in adults
Authors: Fukuhara Kei , Furihata Kenichi , Matsuoka Nobushige , Itamura Rio , Ramos Vesper , Hagi Toshiaki , Kalluru Hindu , Bramson Candace , Terra Steven G. , Liu Jing 
Published: April 2023

AbstractVupanorsen (PF‐07285557) is a second‐generation tri‐N‐acetyl galactosamine (GalNAc3)‐antisense oligonucleotide targeted to angiopoietin‐like 3 (ANGPTL3) mRNA, shown to reduce lipids and apolipoproteins in subjects with dyslipidemia. To aid bringing innovative drugs to global patients efficiently, a multi‐purpose Japanese phase I study was conducted, with integrated development approaches agreed by the Pharmaceuticals and Medical Devices Agency (PMDA). This randomized, double‐blind, placebo‐controlled, single‐ascending dose (SAD) study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of vupanorsen administered subcutaneously to Japanese adults (20–65 years) with elevated triglycerides (TG). Participants were randomized (1:1:1) to vupanorsen (80:160 mg) or placebo (N = 4 each). Vupanorsen 160 mg was a first‐in‐human (FIH) dose level. Vupanorsen was well‐tolerated with no treatment‐related adverse events reported for either dose. Absorption into the systemic circulation was rapid with median time to maximum concentration (Tmax) of 3.5 and 2.0 h, for vupanorsen 80 and 160 mg, respectively. Following maximum concentration (Cmax), vupanorsen underwent multiphasic decline characterized by a relatively fast initial distribution phase followed by slower terminal elimination phase, with elimination half‐life (t1/2) of 397 and 499 h (80, 160 mg), respectively. Area under the concentration–time curve (AUC) and Cmax increased in a greater than dose‐proportional manner. Pharmacodynamic markers (ANGPTL3, TG, and other key lipids) were reduced with vupanorsen versus placebo. Vupanorsen was safe and well‐tolerated in healthy Japanese participants with elevated TG. This study provided FIH data for vupanorsen 160 mg. Moreover, the SAD study in Japanese participants fulfilled PMDA bridging requirements, and with the totality of global vupanorsen data, supported the PMDA waiver for a local phase II dose‐finding study. ClinicalTrials.gov: NCT04459767.
Palmitate alters miR‐2137 and miR‐503‐5p to induce orexigenic Npy in hypothalamic neuronal cell models: Rescue by oleate and docosahexaenoic acid
Authors: McIlwraith Emma K. , Belsham Denise D. 
Published: April 2023

AbstractMicroRNAs (miRNAs) are short noncoding RNA implicated in the pathogenesis of obesity. One cause of obesity is excess exposure to the saturated fatty acid palmitate that can alter miRNA levels in the periphery. Palmitate also promotes obesity by acting on the hypothalamus, the central coordinator of energy homeostasis, to dysregulate hypothalamic feeding neuropeptides and induce ER stress and inflammatory signaling. We hypothesized that palmitate would alter hypothalamic miRNAs that control genes involved in energy homeostasis thereby contributing to the obesity‐promoting effects of palmitate. We found that palmitate upregulated 20 miRNAs and downregulated six miRNAs in the orexigenic NPY/AgRP‐expressing mHypoE‐46 cell line. We focused on delineating the roles of miR‐2137 and miR‐503‐5p, as they were strongly up‐ and downregulated by palmitate, respectively. Overexpression of miR‐2137 increased Npy mRNA levels and downregulated Esr1 levels, while increasing C/ebpβ and Atf3 mRNA. Inhibiting miR‐2137 had the opposite effect, except on Npy, which was unchanged. The most downregulated miRNA by palmitate, miR‐503‐5p, negatively regulated Npy mRNA levels. Exposure to the unsaturated fatty acids oleate or docosahexaenoic acid completely or partially blocked the effects of palmitate on miR‐2137 and miR‐503‐5p as well as Npy, Agrp, Esr1, C/ebpβ and Atf3. MicroRNAs may therefore contribute to palmitate actions in dysregulating NPY/AgRP neurons. Effectively combating the deleterious effects of palmitate is crucial to help prevent or reduce the impact of obesity.
Supplemental Figures and Tables from Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer
Authors: Varadan Vinay , Gilmore Hannah , Miskimen Kristy L.S. , Tuck David , Parsai Shikha , Awadallah Amad , Krop Ian E. , Winer Eric P. , Bossuyt Veerle , Somlo George , Abu-Khalaf Maysa M. , Fenton Mary Anne , Sikov William , Harris Lyndsay N. 
Published: April 2023

<p>Supplemental Figure 1.	Consort Diagram 03-311. Supplemental Figure 2.	Consort Diagram 211B. Supplemental Figure 3.	Subtype-specific changes in Immune Index upon brief-exposure to nab-paclitaxel in the 211B trial. Supplemental Figure 4. Evaluation of the Immune Index upon brief-exposure to trastuzumab in the 03-311 and 211B trials according to ER/PR status. Supplemental Figure 5. Evaluation of the Immune Index upon brief-exposure to nab-paclitaxel in the 211B trial according to ER/PR status. Supplemental Figure 6. Correlation between Immune Index and tumor content. Supplemental Figure 7. Association of CD4+ Th1 and Treg signatures with response. Supplemental Table 1.	Immune Index genes discriminative of response at the post-exposure timepoint in the discovery (03-311) and validation (211B) datasets. Supplemental Table 2.	Immune cell subset signatures discriminative of response at baseline and post-exposure timepoints in the discovery (03-311) and validation (211B) datasets. Supplemental Table 3.	CD8+ T-cell cytolytic activity genes discriminative of response at the post-exposure timepoint in the discovery (03-311) and validation (211B) datasets.</p>
Figure A3 from Expression of Five Neuroblastoma Genes in Bone Marrow or Blood of Patients with Relapsed/Refractory Neuroblastoma Provides a New Biomarker for Disease and Prognosis
Authors: Marachelian Araz , Villablanca Judith G. , Liu Cathy W. , Liu Betty , Goodarzian Fariba , Lai Hollie A. , Shimada Hiroyuki , Tran Hung C. , Parra Jaime A. , Gallego Richard , Bedrossian Nora , Young Sabrina , Czarnecki Scarlett , Kennedy Rebekah , Weiss Brian D. , Goldsmith Kelly , Granger Meaghan , Matthay Katherine K. , Groshen Susan , Asgharzadeh Shahab , Sposto Richard , Seeger Robert C. 
Published: April 2023

<p>Comparison of 1 year EFS in two groups defined by a range of Ã¢Ë†â€ CT cut points (left column) and corresponding ROC analysis of the ability of Ã¢Ë†â€ CT values above the cutpoint to predict 1 year EFS (right column), for assays based on different combinations of genes. NB5 assay (A, B), Phox2B/TH/DDC (C, D), Phox2B/TH (E, F), Phox2B/TH/Dcx (G, H), Th/Dcx (I, J). These analyses show that the NB5 assay is at least as or more predictive then the other gene combinations.</p>
Figure S1, Figure S2, Figure S3, Figure S4, Figure S5, Figure S6 from Phase Ib Study of Lumretuzumab Plus Cetuximab or Erlotinib in Solid Tumor Patients and Evaluation of HER3 and Heregulin as Potential Biomarkers of Clinical Activity
Authors: Meulendijks Didier , Jacob Wolfgang , Voest Emile E. , Mau-Sorensen Morten , Martinez-Garcia Maria , Taus Alvaro , Fleitas Tania , Cervantes Andres , Lolkema Martijn P. , Langenberg Marlies H.G. , De Jonge Maja J. , Sleijfer Stefan , Han Ji-Youn , Calles Antonio , Felip Enriqueta , Kim Sang-We , Schellens Jan H.M. , Wilson Sabine , Thomas Marlene , Ceppi Maurizio , Meneses-Lorente Georgina , James Ian , Vega-Harring Suzana , Dua Rajiv , Nguyen Maitram , Steiner Lori , Adessi Celine , Michielin Francesca , Bossenmaier Birgit , Weisser Martin , Lassen Ulrik N. 
Published: April 2023

<p>Supplementary Figure 1	Quantile plots of baseline membrane HER3 IRS score (A) and HER3 mRNA log expression (B) in baseline FFPE tumor biopsy samples from patients with known adeno- and squamous cell carcinoma histology Supplementary Figure 2	Quantile plots of baseline membrane HER3 immuno-reactive scores in fresh FFPE tumor biopsies from NSCLC patients with non-squamous or squamous histology Supplementary Figure 3	Quantile plots of baseline HRG mRNA log expression determined by qRT-PCR in FFPE tumor biopsies of adeno- and squamous cell carcinoma histology (data obtained using the HRG research assay) Supplementary Figure 4	Baseline HRG mRNA log expression in FFPE tumor biopsies, determined by qRT-PCR, in non-sqNSCLC and sqNSCLC (data obtained using the HRG prototype diagnostic assay). Dotted line indicates prior determined median HRG expression in sqNSCLC. Supplementary Figure 5	Best percentage change from baseline in sum of longest diameters of target lesions for patients in the dose escalation and extension phase of the cetuximab part (n = 38). Red bars indicate PD patients, blue bars SD patients, light green bars PR patients and dark green bars CR patients. Eleven patients were without target lesion assessment post baseline. Tumor type and lumretuzumab dose are indicated. * indicates patients who received previous EGFR-targeting therapy. a indicates a patient who received prior trastuzumab therapy. Supplementary Figure 6	Best percentage change from baseline in sum of longest diameters of target lesions for patients in the dose escalation phase and the two NRG1 fusion gene patients of the extension phase of the erlotinib part (n = 31). Red bars indicate PD patients, blue bars SD patients and green bars PR patients. Eight patients were without target lesion assessment post baseline. Tumor type and lumretuzumab dose are indicated. * indicates patients who received previous EGFR-targeting therapy. a indicates two patients with NRG1 gene fusion.</p>
Supp Figure 1 from Expression of PD-1 by T Cells in Malignant Glioma Patients Reflects Exhaustion and Activation
Authors: Davidson Tom B. , Lee Alexander , Hsu Melody , Sedighim Shaina , Orpilla Joey , Treger Janet , Mastall Max , Roesch Saskia , Rapp Carmen , Galvez Mildred , Mochizuki Aaron , Antonios Joseph , Garcia Alejandro , Kotecha Nikesh , Bayless Nicholas , Nathanson David , Wang Anthony , Everson Richard , Yong William H. , Cloughesy Timothy F. , Liau Linda M. , Herold-Mende Christel , Prins Robert M. 
Published: April 2023

<p>Supplementary Figure 1: T cells from GBM patient TILs show highest expression of PD-1 compared to healthy donor PBMC and GBM patient PBMCs A)	A representative flow cytometry plot measuring PD-1+ expression on CD4+ and CD8+ T cells from Healthy Donor PBMC, glioma Patient PBMC, and glioma patient TILs. B)	Percent of PD-1 expression on CD4+ T cells from all the patient samples as measured by flow cytometry. C)	Percent of PD-1 expression on CD8+ T cell from all the patient samples as measured by flow cytometry.</p>