Prospectus, October 28, 1981

SENIORS VISIT PARKLAND; News In Brief; Donate blood--help others: One that was helped; Gazette to go electronic; Get on P.C. blood donor team; Images: students at creative best; Homecoming idea conceived by 2 bored men; Western look phasing out; \u27Antigone\u27 opens Nov. 12; County moves to METCAD; Spend year abroad, see Scandinavia; Be safe on Halloween; Stories welcome; P.C. Happ\u27nin\u27s: Ski club plans finances, Prayers offered, EMT workshop set, Model ships presented, CHI sponsors program, Encouraging parents, Stugo discusses food; Chief Illiniwek -- Part of Illini tradition; Moody Blues: classic; Halloween hits early; Willie Nesbit wins Freddy contest; Sports Notes; Girls open at Sugar Grove; Illini football pleases fan; Fast Freddy Contest; Correction; \u27Gallipoli\u27 deals with war, friendship, death; Classifieds; Duvall stars in \u27Confessions\u27; \u27Marbles\u27: nice surprise; Library plans A-V Week; Laugh at \u27Merlin\u27https://spark.parkland.edu/prospectus_1981/1007/thumbnail.jp

A pilot study of nintedanib in molecularly selected patients with advanced non-small cell lung cancer

BACKGROUND: Nintedanib is a small molecule tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). The purpose of the study was to evaluate the response rate for patients with advanced non-small cell lung cancer (NSCLC) with mutations in METHODS: Patients with advanced NSCLC previously treated with platinum-doublet chemotherapy with the above mutations were enrolled. Exclusion criteria included necrotic tumors with invasion of blood vessels, history of recent thromboembolic events, increased risk of bleeding or thrombosis, myocardial infarction, and weight loss \u3e10% within past 6 months. Nintedanib was administered at a dose of 200 mg orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary endpoints included progression-free survival (PFS) and correlating outcomes with specific mutations. This study was registered with ClinicalTrials.gov, number NCT02299141. RESULTS: Between 2015 and 2019, 20 patients were enrolled with a median age was 66 years, 15 (75%) were females, 15 (75%) had adenocarcinoma, and 17 patients had a CONCLUSIONS: In this pilot study in heavily pretreated and molecularly selected patients with metastatic NSCLC, nintedanib showed modest activity

Genomic complexity predicts resistance to endocrine therapy and CDK4/6 inhibition in hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer

PURPOSE: Clinical biomarkers to identify patients unlikely to benefit from CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) are lacking. We implemented a comprehensive circulating tumor DNA (ctDNA) analysis to identify genomic features for predicting and monitoring treatment resistance. EXPERIMENTAL DESIGN: ctDNA was isolated from 216 plasma samples collected from 51 patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC) on a phase II trial of palbociclib combined with letrozole or fulvestrant (NCT03007979). Boosted whole-exome sequencing (WES) was performed at baseline and clinical progression to evaluate genomic alterations, mutational signatures, and blood tumor mutational burden (bTMB). Low-pass whole-genome sequencing was performed at baseline and serial timepoints to assess blood copy-number burden (bCNB). RESULTS: High bTMB and bCNB were associated with lack of clinical benefit and significantly shorter progression-free survival (PFS) compared with patients with low bTMB or low bCNB (all P \u3c 0.05). Dominant APOBEC signatures were detected at baseline exclusively in cases with high bTMB (5/13, 38.5%) versus low bTMB (0/37, 0%; P = 0.0006). Alterations in ESR1 were enriched in samples with high bTMB (P = 0.0005). There was a high correlation between bTMB determined by WES and bTMB determined using a 600-gene panel (R = 0.98). During serial monitoring, an increase in bCNB score preceded radiographic progression in 12 of 18 (66.7%) patients. CONCLUSIONS: Genomic complexity detected by noninvasive profiling of bTMB and bCNB predicted poor outcomes in patients treated with ET and CDK4/6i and identified early disease progression before imaging. Novel treatment strategies including immunotherapy-based combinations should be investigated in this population

Designing Digital Engagements:Approaches to creative practice and adaptable programming for archaeological visualisation

The processes of archaeological visualisation exist at the intersection of art practice and archaeological interpretation, often involving complex negotiations between stakeholders and practitioners. This paper reflects upon the authors’ experiences developing interactive mixed media content for public outreach from two case study archaeological excavations: the SERF Hillforts Project in Strathearn, Scotland and the Nunalleq Archaeology Project in southwest Alaska. Each presented unique challenges in the integration of layered multivocal narratives in the context of ongoing archaeological excavations. This included evolving scientific interpretations, co-design with stakeholders and a cycle of feedback. Creative design and software development were a core part of the collaborative process that resulted in these interactive digital interfaces. Here we explore how collaborative creative practice influenced the design choices that were made and the programming paradigms that were used

Repeated successful surgical rescues of early and delayed multiple ruptures of ventricular septum, right ventricle and aneurysmal left ventricle following massive biventricular infarction

A 58 year old man underwent 6 surgical interventions for various complications of massive biventricular myocardial infarction over a period of 2 years following acute occlusion of a possibly "hyperdominant" left anterior descending coronary artery. These included concomitant repair of apicoanterior post-infarction VSD and right ventricular free wall rupture, repeat repair of recurrent VSD following inferoposterior extension of VSD in the infarcted septum 5 weeks later, repair of delayed right ventricular free wall rupture 4 weeks subsequently, repair of a bleeding left ventricular aneurysm eroding through left chest wall 16 months thereafter, repair of right upper lobe lung tear causing massive anterior mediastinal haemorrhage, mimicking yet another cardiac rupture, 2 months later, followed, at the same admission, 2 weeks later, by sternal reconstruction for dehisced and infected sternum using pedicled myocutaneous latissimus dorsi flap. 5 years after the latissimus myoplasty, the patient remains in NYHA class 1 and is leading a normal life

Microarray-Based Sketches of the HERV Transcriptome Landscape

Human endogenous retroviruses (HERVs) are spread throughout the genome and their long terminal repeats (LTRs) constitute a wide collection of putative regulatory sequences. Phylogenetic similarities and the profusion of integration sites, two inherent characteristics of transposable elements, make it difficult to study individual locus expression in a large-scale approach, and historically apart from some placental and testis-regulated elements, it was generally accepted that HERVs are silent due to epigenetic control. Herein, we have introduced a generic method aiming to optimally characterize individual loci associated with 25-mer probes by minimizing cross-hybridization risks. We therefore set up a microarray dedicated to a collection of 5,573 HERVs that can reasonably be assigned to a unique genomic position. We obtained a first view of the HERV transcriptome by using a composite panel of 40 normal and 39 tumor samples. The experiment showed that almost one third of the HERV repertoire is indeed transcribed. The HERV transcriptome follows tropism rules, is sensitive to the state of differentiation and, unexpectedly, seems not to correlate with the age of the HERV families. The probeset definition within the U3 and U5 regions was used to assign a function to some LTRs (i.e. promoter or polyA) and revealed that (i) autonomous active LTRs are broadly subjected to operational determinism (ii) the cellular gene density is substantially higher in the surrounding environment of active LTRs compared to silent LTRs and (iii) the configuration of neighboring cellular genes differs between active and silent LTRs, showing an approximately 8 kb zone upstream of promoter LTRs characterized by a drastic reduction in sense cellular genes. These gathered observations are discussed in terms of virus/host adaptive strategies, and together with the methods and tools developed for this purpose, this work paves the way for further HERV transcriptome projects

Lack of Rhesus antigen expression by human committed erythroid progenitors

Abstract The D antigen of the Rhesus blood group, an erythroid-specific cell surface marker, is expressed by all morphologically recognizable human nucleated red blood cell precursors including, in low density, the pronormoblast. The object of the present study was to determine the expression of the D antigen by committed erythroid progenitors. Under conditions that produced complete inhibition of BFU-E and CFU-E by known cytotoxic antisera, no significant inhibition was produced by anti-D. Use of anti-human IgG (rabbit) to increase sensitivity and trypsinization to reveal cryptic Rh determinants were both without inhibitory effect. Erythroid bursts and colonies grew normally in methylcellulose that contained anti-D. The addition of anti-D to day 7 BFU-E did not inhibit their proliferation to mature bursts at day 14. These results suggest that the D antigen is not expressed by human committed erythroid progenitor cells. The D antigen is therefore an erythroid-specific differentiation marker, rather than an erythroid- lineage-specific antigen. The development of expression of the D antigen during erythropoiesis parallels that of band 3 protein, to which anti-D has been reported to bind. Lack of Rh expression by committed erythroid progenitors is consistent with the rarity of red cell aplasia in Rhesus hemolytic disease of the newborn and in idiopathic and drug-induced autoimmune hemolytic anemia in which the autoantibodies have apparent Rh specificity. These results imply that Rh compatibility is not a contraindication to human bone marrow transplantation.</jats:p

Lack of Rhesus antigen expression by human committed erythroid progenitors

The D antigen of the Rhesus blood group, an erythroid-specific cell surface marker, is expressed by all morphologically recognizable human nucleated red blood cell precursors including, in low density, the pronormoblast. The object of the present study was to determine the expression of the D antigen by committed erythroid progenitors. Under conditions that produced complete inhibition of BFU-E and CFU-E by known cytotoxic antisera, no significant inhibition was produced by anti-D. Use of anti-human IgG (rabbit) to increase sensitivity and trypsinization to reveal cryptic Rh determinants were both without inhibitory effect. Erythroid bursts and colonies grew normally in methylcellulose that contained anti-D. The addition of anti-D to day 7 BFU-E did not inhibit their proliferation to mature bursts at day 14. These results suggest that the D antigen is not expressed by human committed erythroid progenitor cells. The D antigen is therefore an erythroid-specific differentiation marker, rather than an erythroid- lineage-specific antigen. The development of expression of the D antigen during erythropoiesis parallels that of band 3 protein, to which anti-D has been reported to bind. Lack of Rh expression by committed erythroid progenitors is consistent with the rarity of red cell aplasia in Rhesus hemolytic disease of the newborn and in idiopathic and drug-induced autoimmune hemolytic anemia in which the autoantibodies have apparent Rh specificity. These results imply that Rh compatibility is not a contraindication to human bone marrow transplantation.</jats:p