Analytical performance of OncoPrism-HNSCC, an RNA-based assay to inform immune checkpoint inhibitor treatment decisions for recurrent/metastatic head and neck squamous cell carcinoma.

Background: While immune checkpoint inhibitor (ICI) therapies can significantly improve outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC), only about 15-20% benefit from such treatments. Clinical tests that guide the use of ICIs are therefore critically needed. OncoPrism-HNSCC was developed to address this need.

Multicenter validation of an RNA-based assay to predict anti-PD-1 disease control in patients with recurrent or metastatic head and neck squamous cell carcinoma: the PREDAPT study.

Background: Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients.

SNAPSHOT USA 2021: A third coordinated national camera trap survey of the United States.

SNAPSHOT USA is a multicontributor, long-term camera trap survey designed to survey mammals across the United States. Participants are recruited through community networks and directly through a website application (https://www.snapshot-usa.

Multidimensional biomarker predicts disease control in response to immunotherapy in recurrent or metastatic head and neck squamous-cell carcinoma.

Purpose: Anti-PD-1 therapy provides clinical benefit in 40-50% of patients with relapsed and/or metastatic head and neck squamous cell carcinoma (RM-HNSCC). Selection of anti- PD-1 therapy is typically based on patient PD-L1 immunohistochemistry (IHC) which has low specificity for predicting disease control. Therefore, there is a critical need for a clinical biomarker that will predict clinical benefit to anti-PD-1 treatment with high specificity.

T cell subtype profiling measures exhaustion and predicts anti-PD-1 response.

Anti-PD-1 therapy can provide long, durable benefit to a fraction of patients. The on-label PD-L1 test, however, does not accurately predict response. To build a better biomarker, we created a method called T Cell Subtype Profiling (TCSP) that characterizes the abundance of T cell subtypes (TCSs) in FFPE specimens using five RNA models.

Analytical Performance of an Immunoprofiling Assay Based on RNA Models.

As immuno-oncology drugs grow more popular in the treatment of cancer, better methods are needed to quantify the tumor immune cell component to determine which patients are most likely to benefit from treatment. Methods such as flow cytometry can accurately assess the composition of infiltrating immune cells; however, they show limited use in formalin-fixed, paraffin-embedded (FFPE) specimens. This article describes a novel hybrid-capture RNA sequencing assay, ImmunoPrism, that estimates the relative percentage abundance of eight immune cell types in FFPE solid tumors.

Substituting ground woody plants for cottonseed hulls in kid goat feedlot diets: growth performance and blood serum chemistry.

Boer × Spanish kid goats (n = 48) were used to evaluate effects of using ground woody products in feedlot diets on growth performance and blood serum chemistry. A completely randomized study design was used with 2 feeding periods (Period 1 = 70% concentrate, days 0 to 26; Period 2 = 86% concentrate, days 27 to 64). Goats were individually fed 1 of 6 diets that differed only by roughage source (n = 4 wether males and 4 females/treatment; initial BW = 22 ± 2 kg): cottonseed hulls (CSH; control) or ground wood consisting of redberry (RED), blueberry (BLUE), one-seed (ONE), or eastern red cedar (ERC) Juniperus spp.

Substituting ground woody plants for cottonseed hulls in lamb feedlot diets: carcass characteristics, adipose tissue fatty acid composition, and sensory panel traits.

Effects of using ground woody plants in Rambouillet wether lamb (n = 48) feedlot diets on carcass characteristics, adipose tissue fatty acid composition, and sensory panel traits were evaluated. In a randomized design study with two feeding periods (period 1 = fed a 70% concentrate diet from days 0 to 27; period 2 = fed an 86% concentrate diet from days 28 to 57), lambs were individually fed six diets that differed only by roughage source (n = 8 animals/treatment; initial BW = 32.9 ± 3.

Substituting ground woody plants for cottonseed hulls in lamb feedlot diets: Growth performance, blood serum chemistry, and rumen fluid parameters.

Effects of using ground woody plants in Rambouillet wether lamb feedlot diets on growth performance, blood serum, and rumen parameters were evaluated. A randomized design study was used with 2 feeding periods (70% concentrate diet from d 0 to 27 [Period 1] and 86% concentrate diet from d 28 to 57 [Period 2]); the concentrate portion of the diets mainly consisted of dried distiller's grains with solubles and sorghum grain. Lambs were individually fed 6 diets that differed only by roughage source ( = 8 animals/treatment; 32.

A large microRNA cluster on chromosome 19 is a transcriptional hallmark of WHO type A and AB thymomas.

Background: Thymomas are one of the most rarely diagnosed malignancies. To better understand its biology and to identify therapeutic targets, we performed next-generation RNA sequencing.

Methods: The RNA was sequenced from 13 thymic malignancies and 3 normal thymus glands.

Evidence for extensive horizontal gene transfer from the draft genome of a tardigrade.

Horizontal gene transfer (HGT), or the transfer of genes between species, has been recognized recently as more pervasive than previously suspected. Here, we report evidence for an unprecedented degree of HGT into an animal genome, based on a draft genome of a tardigrade, Hypsibius dujardini. Tardigrades are microscopic eight-legged animals that are famous for their ability to survive extreme conditions.

Using RNA Sequencing and In Silico Subtraction to Identify Resistance Gene Analog Markers for Lr16 in Wheat.

Leaf rust, caused by Puccinia triticina Eriks., is one of the most widespread diseases of wheat and breeding for resistance is one of the most effective methods of control. Lr16 is a wheat leaf rust resistance gene (R-gene) that provides resistance at both the seedling and adult stages.

Bovine exome sequence analysis and targeted SNP genotyping of recessive fertility defects BH1, HH2, and HH3 reveal a putative causative mutation in SMC2 for HH3.

The recent discovery of bovine haplotypes with negative effects on fertility in the Brown Swiss, Holstein, and Jersey breeds has allowed producers to identify carrier animals using commercial single nucleotide polymorphism (SNP) genotyping assays. This study was devised to identify the causative mutations underlying defective bovine embryo development contained within three of these haplotypes (Brown Swiss haplotype 1 and Holstein haplotypes 2 and 3) by combining exome capture with next generation sequencing. Of the 68,476,640 sequence variations (SV) identified, only 1,311 genome-wide SNP were concordant with the haplotype status of 21 sequenced carriers.

Next-generation transcriptome sequencing of the premenopausal breast epithelium using specimens from a normal human breast tissue bank.

Introduction: Our efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. In order to provide the specimens that will facilitate such an understanding, The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center (KTB) was established.

Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing.

Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER, PR, and HER-2). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G.

Evolutionary toggling of the MAPT 17q21.31 inversion region.

Using comparative sequencing approaches, we investigated the evolutionary history of the European-enriched 17q21.31 MAPT inversion polymorphism. We present a detailed, BAC-based sequence assembly of the inverted human H2 haplotype and compare it to the sequence structure and genetic variation of the corresponding 1.

Denaturant-induced expansion and compaction of a multi-domain protein: IgG.

It is generally believed that unfolded or denatured proteins show random-coil statistics and hence their radius of gyration simply scales with solvent quality (or concentration of denaturant). Indeed, nearly all proteins studied thus far have been shown to undergo a gradual and continuous expansion with increasing concentration of denaturant. Here, we use fluorescence correlation spectroscopy (FCS) to show that while protein A, a multi-domain and predominantly helical protein, expands gradually and continuously with increasing concentration of guanidine hydrochloride (GdnHCl), the F(ab')2 fragment of goat anti-rabbit antibody IgG, a multi-subunit all beta-sheet protein does not show such continuous expansion behavior.

Using an amino acid fluorescence resonance energy transfer pair to probe protein unfolding: application to the villin headpiece subdomain and the LysM domain.

Previously, we have shown that p-cyanophenylalanine (Phe CN) and tryptophan (Trp) constitute an efficient fluorescence resonance energy transfer (FRET) pair that has several advantages over commonly used dye pairs. Here, we aim to examine the general applicability of this FRET pair in protein folding-unfolding studies by applying it to the urea-induced unfolding transitions of two small proteins, the villin headpiece subdomain (HP35) and the lysin motif (LysM) domain. Depending on whether Phe CN is exposed to solvent, we are able to extract either qualitative information about the folding pathway, as demonstrated by HP35, which has been suggested to unfold in a stepwise manner, or quantitative thermodynamic and structural information, as demonstrated by LysM, which has been shown to be an ideal two-state folder.

Whole-genome sequencing and variant discovery in C. elegans.

Massively parallel sequencing instruments enable rapid and inexpensive DNA sequence data production. Because these instruments are new, their data require characterization with respect to accuracy and utility. To address this, we sequenced a Caernohabditis elegans N2 Bristol strain isolate using the Solexa Sequence Analyzer, and compared the reads to the reference genome to characterize the data and to evaluate coverage and representation.

Gallus GBrowse: a unified genomic database for the chicken.

Gallus GBrowse (http://birdbase.net/cgi-bin/gbrowse/gallus/) provides online access to genomic and other information about the chicken, Gallus gallus. The information provided by this resource includes predicted genes and Gene Ontology (GO) terms, links to Gallus In Situ Hybridization Analysis (GEISHA), Unigene and Reactome, the genomic positions of chicken genetic markers, SNPs and microarray probes, and mappings from turkey, condor and zebra finch DNA and EST sequences to the chicken genome.

Evolutionary and biomedical insights from the rhesus macaque genome.

The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families.

The impact of laparoscopic bariatric workshops on the practice patterns of surgeons.

Background: This study was designed to evaluate the impact of a 2-day laparoscopic bariatric workshop on the practice patterns of participating surgeons.

Methods: From October 1998 to June 2002, 18 laparoscopic bariatric workshops were attended by 300 surgeons. Questionnaires were mailed to all participants.