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The molecular signature response classifier (MSRC) predicts tumor necrosis factor-ɑ inhibitor (TNFi) non-response in rheumatoid arthritis. This study evaluates decision-making, validity, and utility of MSRC testing. This comparative cohort study compared an MSRC-tested arm (N = 627) from the Study to Accelerate Information of Molecular Signatures (AIMS) with an external control arm (N = 2721) from US electronic health records. Propensity score matching was applied to balance baseline characteristics. Patients initiated a biologic/targeted synthetic disease-modifying antirheumatic drug, or continued TNFi therapy. Odds ratios (ORs) for six-month response were calculated based on clinical disease activity index (CDAI) scores for low disease activity/remission (CDAI-LDA/REM), remission (CDAI-REM), and minimally important differences (CDAI-MID). In MSRC-tested patients, 59% had a non-response signature and 70% received MSRC-aligned therapy. In TNFi-treated patients, the MSRC had an 88% PPV and 54% sensitivity. MSRC-guided patients were significantly (p < 0.0001) more likely to respond to b/tsDMARDs than those treated according to standard care (CDAI-LDA/REM: 36.0% vs 21.9%, OR 2.01[1.55–2.60]; CDAI-REM: 10.4% vs 3.6%, OR 3.14 [1.94–5.08]; CDAI-MID: 49.5% vs 32.8%, OR 2.01[1.58–2.55]). MSRC clinical validity supports high clinical utility: guided treatment selection resulted in significantly superior outcomes relative to standard care; nearly three times more patients reached CDAI remission. Clinicians can offer rheumatoid arthritis patients many types of therapies but the response rate for each of these drugs is low. For example, within the first year of treatment, just about one-half of patients respond to the first-line drug, csDMARD. Only one-third of methotrexate-unresponsive patients will respond to the most common second-line agent, a tumor necrosis factor-α inhibitor. These low response rates present a critical challenge to treating patients. Clinicians try different cs- and b/tsDMARD and fail to quickly identify the most effective options. Then, disease will progress, irreversibly destroying patient joints, diminishing patient health-related quality of life, and increasing risks of cardiovascular disease, cancer, and death. To help clinicians quickly identify the best drugs for patients in a treat-to-target approach, a precision-medicine test was developed to identify patients unlikely to respond to tumor necrosis factor-α inhibitors. This molecular signature response classifier considers both molecular features (patient RNA-expression levels) and clinical features (e.g. body mass index, sex) to predict patient response. To evaluate the effectiveness of this test, the outcomes of patients treated with classifier-selected drugs (in a large, tested cohort) were compared with outcomes of patients treated with conventionally selected therapies (in an external cohort of electronic-health-record data). Patients treated with classifier-selected therapies were approximately three times as likely to achieve remission than were patients treated with conventionally selected drugs. These results suggest that this molecular signature response classifier is a valuable tool for more quickly identifying optimal therapies to treat rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Native chicken in India assumes a significant role in contemplating rural economy. The local birds play a major role in providing subsidiary income and nutritional security to the people of India. A total of 19 native chicken breeds have been reported and registered in India by ICAR-National Bureau of Animal Genetic Resources, Karnal, India, which is the nodal agency of Government of India for registering breeds of livestock and poultry. At present, the Indian native chicken population is 37.2% of the total poultry population, which contribute around 17.8% of the total egg production in the country. The Indian birds have many unique traits such as natural broodiness to hatch chicks, better adaptability to hot and humid tropical climate, resilience to some of the deadly diseases such as Newcastle disease, IBD etc., black coloured meat of Kadaknath chicken, running fast and flying, fighting habit to protect themselves from the predators, tenderness of meat similar to red meat, low mortality at high temperature and humidity when exotic birds mostly die, survival on scavenging and perform at low input diet. The major objective of this paper is to compile the characteristics of Indian native chicken breeds comprehensively so that by going through this article, the stakeholders may categorise any birds of India in a particular indigenous breed group or any other group or non-descript groups. In this article, we reviewed signature of Indian chickens to differentiate them from the exotic and other breeds of chicken. We have delineated phenotypes and molecular parameters of Indian chickens along with their performances. We have deciphered genetic distance of some of the Indian chickens from the exotic chickens revealing their unique position in the cluster. It is concluded that the breed signature has potential to distinguish Indian chicken population from exotic ones for the breed identity. [ABSTRACT FROM AUTHOR]

The molecular signature response classifier (MSRC) is a blood-based precision medicine test that predicts nonresponders to tumor necrosis factor-ɑ inhibitors (TNFi) in rheumatoid arthritis (RA) so that patients with a molecular signature of non-response to TNFi can be directed to a treatment with an alternative mechanism of action. This study evaluated decision choice and treatment outcomes resulting from MSRC-informed treatment selection within a real-world cohort. Therapy selection by providers was informed by MSRC results for 73.5% (277/377) of patients. When MSRC results were not incorporated into decision-making, 62.0% (62/100) of providers reported deviating from test recommendations due to insurance-related restrictions. The 24-week ACR50 responses in patients prescribed a therapy in alignment with MSRC results were 39.6%. Patients with a molecular signature of non-response had significantly improved responses to non-TNFi therapies compared with TNFi therapies (ACR50 34.8% vs 10.3%, p-value = 0.05). This indicates that predicted non-responders to TNFi therapies are not nonresponders to other classes of RA targeted therapy. Significant changes were also observed for CDAI, ACR20, ACR70, and for responses at 12 weeks. Adoption of the MSRC into patient care could fundamentally shift treatment paradigms in RA, resulting in substantial improvements in real-world treatment outcomes. [ABSTRACT FROM AUTHOR]

Angiogenesis is in a constant balance between pro and anti-angiogenic factors. Neoangiogenesis, implicated in metastatic spreading is characterized in solid cancers, but fairly new in chronic lymphocytic leukemia (CLL). We hypothesize that secretion of angiogenic factors could be correlated to the pathogenesis of CLL, and therefore predict the outcome of patients. We investigated concentrations of 22 cytokines and chemokines in 137 non-del 17p B-CLL patients, treated with a fludarabine-cyclophosphamide-rituximab (FCR)-based regimen. We constructed a biomarker index defining different risk groups based on lymphocyte count, the intensity of CD20 antigen on CD19+ cells, Ang-2, and PDGF-BB plasma concentrations at diagnosis. Four groups were defined, exhibiting specific molecular signatures and correlated with progression-free survival of patients. Our results suggest that we can determine at diagnosis of non-del 17p B-CLL patients, those with a very high probability of progression-free survival, independently of IGVH mutational status and residual disease at the end of treatment. [ABSTRACT FROM AUTHOR]

We performed gene expression profiling in Epstein–Barr virus (EBV)-associated T/natural killer (NK)-cell lymphoproliferative disorder in children and young adults (TNKLPDC) in order to understand the molecular pathways deregulated in this disease and compared it with nasal-type NK/T-cell lymphoma (NKTL). The molecular and phenotypic signature of TNKLPDC is similar to NKTL, with overexpression of p53, survivin and EZH2. Down-regulation of EZH2 in TNKLPDC cell lines led to an increase in apoptosis and decrease in tumor viability, suggesting that EZH2 may be important for the survival of TNKLPDC cells and hence potentially a useful therapeutic target. Notably, our gene expression profiling revealed a distinctive enrichment of stem cell related genes in TNKLPDC compared to NKTL. This was validated by a significantly higher expression of aldehyde dehydrogenase 1 (ALDH1) in TNKLPDC cell lines compared to NKTL cell lines. The novel discovery of cancer stem cell properties in TNKLPDC has potential therapeutic implications in this group of disorders. [ABSTRACT FROM PUBLISHER]

Objective: Investigation on whether the characteristic molecular signatures can discriminate individual volatile organic compounds (VOCs) and provide predictive markers for the detection of VOC exposure. Methods: Transcriptomic analysis of liver tissues was performed 48 h after the single oral administration of three VOCs doses at LD25 or LD5 values, to Sprague-Dawley. Results: Combination analysis of different multi-classifications suggested that 145 genes predicted VOC exposure. Additionally, Gene Set Enrichment Analysis of genes deregulated by VOCs revealed that T cell prolymphatic leukemia signaling was inactivated in all VOCs. Conclusions: These molecular markers could be widely implemented to assess and predict environmental exposure to VOCs. [ABSTRACT FROM AUTHOR]

A major challenge for molecular diagnosis of bladder cancer is the subdivision of tumors beyond histological classifications into clinical relevant molecular subgroups. The evolution of molecular high-throughput techniques assessing a large number of molecular features at the same time has made comprehensive investigation of these subgroups possible. Molecular signatures for disease stage, grade, progression, carcinoma in situ, presence of metastases, and treatment response have been reported. Some of these molecular signatures are now being tested in multicenter studies with the purpose of introducing these into the clinic, for planning of follow-up and treatment selection. In this review, we define the clinical relevant subgroups and give an overview of recent advances in marker identification in the field of non-muscle invasive and invasive bladder cancer. Furthermore, we stress the methods and materials needed to translate such molecular profiles into clinically useful tests. [ABSTRACT FROM AUTHOR]

A major challenge for molecular diagnosis of bladder cancer is the subdivision of tumors beyond histological classifications into clinical relevant molecular subgroups. The evolution of molecular high-throughput techniques assessing a large number of molecular features at the same time has made comprehensive investigation of these subgroups possible. Molecular signatures for disease stage, grade, progression, carcinoma in situ, presence of metastases, and treatment response have been reported. Some of these molecular signatures are now being tested in multicenter studies with the purpose of introducing these into the clinic, for planning of follow-up and treatment selection. In this review, we define the clinical relevant subgroups and give an overview of recent advances in marker identification in the field of non-muscle invasive and invasive bladder cancer. Furthermore, we stress the methods and materials needed to translate such molecular profiles into clinically useful tests. [ABSTRACT FROM AUTHOR]

The sustained mass production of alevins in finfish aquaculture requires a deep understanding of the biological processes controlling gametogenesis, which ultimately will determine the quality of eggs and sperm. Functional genomics and proteomics technologies have been recently developed, expanding the scope of biological investigation from studying single genes or proteins to studying potentially all genes and proteins at once in a systematic manner. The application of these methods in aquaculture is still in its infancy, especially with regard to the study of fish reproduction, but in the near future its impact is envisaged because of their potential to uncover the complex genetic control of gamete formation. Here, we review recent studies employing high-throughput genomics and proteomics approaches that have been carried out to investigate the global pattern of gene and protein expression during finfish gametogenesis. The results of these studies have already identified a number of novel genes, maternal molecules, and proteins that may be essential during spermatogenesis, oogenesis, and early embryogenesis, thus greatly contributing to our current knowledge of the molecular mechanisms underlying egg and sperm formation. The full potential of genomics to uncover the molecular basis of fish gametogenesis is about to be unleashed with the sequencing of the genome and transcriptome of additional species and the development of methods to elucidate gene function. [ABSTRACT FROM AUTHOR]

Microbial forensics is a new discipline combining microbiology and forensic science. Unlike public health investigations, microbial forensics goes further to associate the source of the causative agent with a specific individual or group. Microbial forensics measures molecular variations between related microbial strains and their use to infer the origin, relationship, or transmission route of a particular microbial strain. Several advanced molecular techniques and practices including molecular phylogeny, whole genome sequencing, microarray analysis, and DNA fingerprinting offer reliable results for interpretation in a microbial forensic investigation. Results from such analyses may be related to the intentional use of microbial agents for bioterrorism or the accidental release of any offensive microorganisms or toxins of public health importance specifically for the purpose of determining the origin. Thus, the new discipline of microbial forensics is an integration of an array of well-established fields, such as microbial genomics, phylogenetics, forensic informatics, and classical microbiology. In this article, we review the concept, technology base, success stories, and challenges of microbial forensics and its application in bioterrorism-related investigations. [ABSTRACT FROM AUTHOR]

Chronic inflammatory skin diseases such as psoriasis and eczema are a major medical challenge. Development of highly specific therapies for both conditions is opposed by the lack of translation of basic knowledge into biomarkers for clinical use. Furthermore, to distinguish psoriasis from eczema might be difficult occasionally, but specific and costly therapies would not be efficient in misdiagnosed patients. In the era of high-throughput 'omics'-technologies, comparing the molecular signature of psoriasis and eczema is a promising approach to gain insight into their complex pathogeneses and develop new diagnostic and therapeutic strategies. Investigating patients affected by both psoriasis and eczema simultaneously, we recently constructed a disease classifier consisting of only two genes (NOS2 and CCL27) that reliably predicts the correct diagnosis even in clinically unclear cases. When such easy-to-handle approaches are combined with individual therapeutic response, we might reach the ultimate goal of personalized medicine in inflammatory skin diseases in near future. [ABSTRACT FROM AUTHOR]