The salivary metatranscriptome as an accurate diagnostic indicator of oral cancer.

Despite advances in cancer treatment, the 5-year mortality rate for oral cancers (OC) is 40%, mainly due to the lack of early diagnostics. To advance early diagnostics for high-risk and average-risk populations, we developed and evaluated machine-learning (ML) classifiers using metatranscriptomic data from saliva samples (n = 433) collected from oral premalignant disorders (OPMD), OC patients (n = 71) and normal controls (n = 171). Our diagnostic classifiers yielded a receiver operating characteristics (ROC) area under the curve (AUC) up to 0.

Gut Microbiome Activity Contributes to Prediction of Individual Variation in Glycemic Response in Adults.

Limiting postprandial glycemic response (PPGR) is an important intervention in reducing the risk of chronic metabolic diseases and has been shown to impart significant health benefits in people with elevated levels of blood sugar. In this study, we collected gut microbiome activity data by assessing the metatranscriptome, and we measured the glycemic responses of 550 adults who consumed more than 30,000 meals, collectively, from omnivore or vegetarian/gluten-free diets. We demonstrate that gut microbiome activity, anthropometric factors, and food macronutrients modulate individual variation in glycemic response.

[Kidney transplantation from Covid-19 positive deceased donor: what are the consequences for recipients?].

Introduction: In recent months, with the spread of COVID 19, the number of kidney transplants from deceased donors has declined significantly in most countries. One of the reasons is the possibility of infection of the recipient with SARS-CoV-2. Determining the risk of transmission of COVID 19 with a donor organ is very important for developing a kidney transplantation policy during a pandemic.

Kidney transplantation from COVID-19 deceased donor.

We present first known case of kidney transplantation from deceased donor who was retrospectively diagnosed with COVID-19. The recipient hadn't febrile and no other symptoms of acute respiratory disease during all hospital stay. No serum anti-SARS-CoV-2 IgM, IgG were detected before and during 6 weeks after surgery.

Is Kidney Transplantation From a COVID-19-Positive Deceased Donor Safe for the Recipient?

Introduction: In recent months, the number of kidney transplants from deceased donors has declined significantly. One of the reasons is the possibility of infection of the recipient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Determining the risk of transmission of coronavirus disease 2019 (COVID-19) with a donor organ is very important for developing a kidney transplantation policy during a pandemic.

A clinically validated human capillary blood transcriptome test for global systems biology studies.

To prevent and treat chronic diseases, including cancer, a global application of systems biology is needed. We report here a whole blood transcriptome test that needs only 50 μl of capillary (fingerprick) blood. This test is suitable for global applications because the samples are preserved at ambient temperature for up to 4 weeks and the RNA preservative inactivates all pathogens, enabling safe transportation.

A Robust Metatranscriptomic Technology for Population-Scale Studies of Diet, Gut Microbiome, and Human Health.

A functional readout of the gut microbiome is necessary to enable precise control of the gut microbiome's functions, which support human health and prevent or minimize a wide range of chronic diseases. Stool metatranscriptomic analysis offers a comprehensive functional view of the gut microbiome, but despite its usefulness, it has rarely been used in clinical studies due to its complexity, cost, and bioinformatic challenges. This method has also received criticism due to potential intrasample variability, rapid changes, and RNA degradation.

A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases.

Background: A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published.

Objectives: We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases.

The transcription factor ATF2 promotes melanoma metastasis by suppressing protein fucosylation.

Melanoma is one of the most lethal skin cancers worldwide, primarily because of its propensity to metastasize. Thus, the elucidation of mechanisms that govern metastatic propensity is urgently needed. We found that protein kinase Cε (PKCε)-mediated activation of activating transcription factor 2 (ATF2) controls the migratory and invasive behaviors of melanoma cells.

Downregulation of the Ubiquitin Ligase RNF125 Underlies Resistance of Melanoma Cells to BRAF Inhibitors via JAK1 Deregulation.

Despite the remarkable clinical response of melanoma harboring BRAF mutations to BRAF inhibitors (BRAFi), most tumors become resistant. Here, we identified the downregulation of the ubiquitin ligase RNF125 in BRAFi-resistant melanomas and demonstrated its role in intrinsic and adaptive resistance to BRAFi in cultures as well as its association with resistance in tumor specimens. Sox10/MITF expression correlated with and contributed to RNF125 transcription.

Reconstitution of the ERG Gene Expression Network Reveals New Biomarkers and Therapeutic Targets in ERG Positive Prostate Tumors.

Background: Despite a growing number of studies evaluating cancer of prostate (CaP) specific gene alterations, oncogenic activation of the ETS Related Gene (ERG) by gene fusions remains the most validated cancer gene alteration in CaP. Prevalent gene fusions have been described between the ERG gene and promoter upstream sequences of androgen-inducible genes, predominantly TMPRSS2 (transmembrane protease serine 2). Despite the extensive evaluations of ERG genomic rearrangements, fusion transcripts and the ERG oncoprotein, the prognostic value of ERG remains to be better understood.

A systems biology strategy for predicting similarities and differences of drug effects: evidence for drug-specific modulation of inflammation in atherosclerosis.

Background: Successful drug development has been hampered by a limited understanding of how to translate laboratory-based biological discoveries into safe and effective medicines. We have developed a generic method for predicting the effects of drugs on biological processes. Information derived from the chemical structure and experimental omics data from short-term efficacy studies are combined to predict the possible protein targets and cellular pathways affected by drugs.

Relationship between gene expression and enhancement in glioblastoma multiforme: exploratory DNA microarray analysis.

Purpose: To determine the difference in gene expression between completely versus incompletely enhancing glioblastoma multiforme (GBM).

Materials And Methods: Gene expression was determined for 52 newly diagnosed GBMs by using DNA microarrays, and the relationship to enhancement pattern and survival was analyzed. This study was approved by the institutional review board and was HIPAA compliant; informed consent was obtained.

Integrated pathway analysis of rat urine metabolic profiles and kidney transcriptomic profiles to elucidate the systems toxicology of model nephrotoxicants.

In this study, approximately 40 endogenous metabolites were identified and quantified by (1)H NMR in urine samples from male rats dosed with two proximal tubule toxicants, cisplatin and gentamicin. The excreted amount of a majority of those metabolites in urine was found to be dose-dependent and exhibited a strong correlation with histopathology scores of overall proximal tubule damage. MetaCore pathway analysis software (GeneGo Inc.

Nutrigenomics: concepts and applications to pharmacogenomics and clinical medicine.

The maintenance of health and the prevention and treatment of chronic diseases are influenced by naturally occurring chemicals in foods. In addition to supplying the substrates for producing energy, a large number of dietary chemicals are bioactive--that is, they alter the regulation of biological processes and, either directly or indirectly, the expression of genetic information. Nutrients and bioactives may produce different physiological phenotypes among individuals because of genetic variability and not only alter health, but also disease initiation, progression and severity.

Distinct transcription profiles of primary and secondary glioblastoma subgroups.

Glioblastomas are invasive and aggressive tumors of the brain, generally considered to arise from glial cells. A subset of these cancers develops from lower-grade gliomas and can thus be clinically classified as "secondary," whereas some glioblastomas occur with no prior evidence of a lower-grade tumor and can be clinically classified as "primary." Substantial genetic differences between these groups of glioblastomas have been identified previously.

MR imaging correlates of survival in patients with high-grade gliomas.

Background And Purpose: For patients with malignant gliomas, clinical data-including age, perioperative Karnofsky Performance Status (KPS), and tumor resection-and tumor imaging features-including necrosis and edema-have been found to correlate with survival. The purpose of this study was to assess the validity of these results and determine whether other imaging features are useful in predicting survival.

Methods: We analyzed the relationship between 15 imaging variables obtained from contrast-enhanced MR imaging scans and survival in patients with grade III (n = 43) and grade IV (n = 110) glioblastoma multiforme (GBM) gliomas.

Positive selection detection in 40,000 human immunodeficiency virus (HIV) type 1 sequences automatically identifies drug resistance and positive fitness mutations in HIV protease and reverse transcriptase.

Drug resistance is a major problem in the treatment of AIDS, due to the very high mutation rate of human immunodeficiency virus (HIV) and subsequent rapid development of resistance to new drugs. Identification of mutations associated with drug resistance is critical for both individualized treatment selection and new drug design. We have performed an automated mutation analysis of HIV Type 1 (HIV-1) protease and reverse transcriptase (RT) from approximately 40,000 AIDS patient plasma samples sequenced by Specialty Laboratories Inc.