Clinical Microbiome Analysis by Mass Spectrometry-Based Metaproteomics.

Mass spectrometry-based proteomics and metaproteomics have long been used in the study of human microbiomes, with the potential of metaproteomics only recently being fully harnessed. This progress is due to the advancements of high-performance mass spectrometers, innovative proteomics strategies, and the development of dedicated bioinformatics tools. In this review, we critically examine the recent technological developments that enhance the application of metaproteomics in clinical microbiome analysis.

RapidAIM 2.0: a high-throughput assay to study functional response of human gut microbiome to xenobiotics.

Our gut microbiome has its own functionalities which can be modulated by various xenobiotic and biotic components. The development and application of a high-throughput functional screening approach of individual gut microbiomes accelerates drug discovery and our understanding of microbiome-drug interactions. We previously developed the rapid assay of individual microbiome (RapidAIM), which combined an optimized culturing model with metaproteomics to study gut microbiome responses to xenobiotics.

Global mortality of chronic liver diseases attributable to Hepatitis B virus and Hepatitis C virus infections from 1990 to 2019 and projections to 2030.

Background: The burden of chronic liver disease (CLD) deaths attributable to the hepatitis B virus (HBV) and hepatitis C virus (HCV) remains unknown. Further research is required to elucidate the extent of this burden in the eventual elimination of these diseases.

Methods: Data on liver cancer, cirrhosis, and other CLD among 204 countries and territories between 1990 and 2019 was extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) published in 2019.

Language outcomes at 18-24 months of preterm infants from US Spanish- and English-speaking homes.

Aim: To evaluate the association of Spanish compared to English primary household language on preterm (PT) infants' language outcomes in the United States and to examine associations with socio-economic factors.

Methods: This was a retrospective cohort of PT infants born <32 weeks gestation from Spanish-speaking (n = 95) and English-speaking homes (n = 1030) born 2005-2019. Language (primary outcome) and cognitive and motor skills (secondary outcomes) were measured using the BSID-III at 18-24 months corrected age.

MetaPep: A core peptide database for faster human gut metaproteomics database searches.

Metaproteomics has increasingly been applied to study functional changes in the human gut microbiome. Peptide identification is an important step in metaproteomics research, with sequence database search (SDS) and spectral library search (SLS) as the two main methods to identify peptides. However, the large search space in metaproteomics studies causes significant challenges for both identification methods.

The Influence of Protein Secretomes of Enterococcus durans on ex vivo Human Gut Microbiome.

The gut microbiome plays a critical role to all animals and humans health. Methods based on ex vivo cultures are time and cost-effective solutions for rapid evaluation of probiotic effects on microbiomes. In this study, we assessed whether the protein secretome from the potential probiotic Enterococcus durans LAB18S grown on fructoligosaccharides (FOS) and galactoligosaccharides (GOS) had specific effects on ex vivo cultured intestinal microbiome obtained from a healthy individual.

The LDL receptor is regulated by membrane cholesterol as revealed by fluorescence fluctuation analysis.

Membrane cholesterol-rich domains have been shown to be important for regulating a range of membrane protein activities. Low-density lipoprotein receptor (LDLR)-mediated internalization of cholesterol-rich LDL particles is tightly regulated by feedback mechanisms involving intracellular sterol sensors. Since LDLR plays a role in maintaining cellular cholesterol homeostasis, we explore the role that membrane domains may have in regulating LDLR activity.

Assumptions in theories of change.

This paper argues that assumptions in a theory of change are the causal connections, events, and conditions that need to be realized for the intervention to work. Using an example of an intervention aimed at improving educational outcomes for girls in a conservative region, two kinds of assumptions are discussed: cause-effect assumptions and causal-link assumptions. Implications for the use of theories of change, including their use in setting causality and the utility of evidence in argument for learning about and testing assumptions are also discussed.

Early postnatal defects in neurogenesis in the 3xTg mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to dementia. The hippocampus, which is one of the sites where neural stem cells reside and new neurons are born, exhibits the most significant neuronal loss in AD. A decline in adult neurogenesis has been described in several animal models of AD.

Application of Bayesian approaches in drug development: starting a virtuous cycle.

The pharmaceutical industry and its global regulators have routinely used frequentist statistical methods, such as null hypothesis significance testing and p values, for evaluation and approval of new treatments. The clinical drug development process, however, with its accumulation of data over time, can be well suited for the use of Bayesian statistical approaches that explicitly incorporate existing data into clinical trial design, analysis and decision-making. Such approaches, if used appropriately, have the potential to substantially reduce the time and cost of bringing innovative medicines to patients, as well as to reduce the exposure of patients in clinical trials to ineffective or unsafe treatment regimens.

An economic and robust TMT labeling approach for high throughput proteomic and metaproteomic analysis.

Multiplexed quantitative proteomics using tandem mass tag (TMT) is increasingly used in -omic study of complex samples. While TMT-based proteomics has the advantages of the higher quantitative accuracy, fewer missing values, and reduced instrument analysis time, it is limited by the additional reagent cost. In addition, current TMT labeling workflows involve repeated small volume pipetting of reagents in volatile solvents, which may increase the sample-to-sample variations and is not readily suitable for high throughput applications.

MetaLab-MAG: A Metaproteomic Data Analysis Platform for Genome-Level Characterization of Microbiomes from the Metagenome-Assembled Genomes Database.

The studies of microbial communities have drawn increased attention in various research fields such as agriculture, environment, and human health. Recently, metaproteomics has become a powerful tool to interpret the roles of the community members by investigating the expressed proteins of the microbes. However, analyzing the metaproteomic data sets at genome resolution is still challenging because of the lack of efficient bioinformatics tools.

Decreased Antibiotic Exposure for Suspected Early-Onset Sepsis in the Neonatal Intensive Care Unit Through Implementation of an Antimicrobial Time-out.

Antimicrobials are among the most frequently prescribed drugs in the neonatal intensive care unit (NICU), although most neonates exposed lack a bacterial infection. Overuse of antimicrobials carries risk to the patient and fosters the development of resistant organisms. Strategic and systematic processes hold promise to limit the unnecessary use of these drugs in this population.

Assessing the Dark Field of Metaproteome.

The human gut microbiome is a complex system composed of hundreds of species, and metaproteomics can be used to explore their expressed functions. However, many lower abundance species are not detected by current metaproteomic techniques and represent the dark field of metaproteomics. We do not know the minimal abundance of a bacterium in a microbiome(depth) that can be detected by shotgun metaproteomics.

Comprehensive Assessment of Functional Effects of Commonly Used Sugar Substitute Sweeteners on Human Gut Microbiome.

The composition and function of the human gut microbiome are often associated with health and disease status. Sugar substitute sweeteners are widely used food additives, although many studies using animal models have linked sweetener consumption to gut microbial changes and health issues. Whether sugar substitute sweeteners directly change the human gut microbiome functionality remains largely unknown.

Randomised controlled trial of maternal infant-directed reading among hospitalised preterm infants.

Aim: A randomised trial to study the impact of a maternal-driven, infant-directed reading intervention on preterm infant language compared with matched controls.

Methods: Infants born at 22-32 weeks in Women & Infants Neonatal Intensive Care were gestationally stratified to a reading intervention (n = 33) or standard care (n = 34). At 32-, 34- and 36-weeks postmenstrual age, 16-h language recordings were obtained in the hospital.

Evaluating live microbiota biobanking using an microbiome assay and metaproteomics.

Biobanking of live microbiota is becoming indispensable for mechanistic and clinical investigations of drug-microbiome interactions and fecal microbiota transplantation. However, there is a lack of methods to rapidly and systematically evaluate whether the biobanked microbiota maintains their cultivability and functional activity. In this study, we use a rapid microbiome assay and metaproteomics to evaluate the cultivability and the functional responses of biobanked microbiota to treatment with a prebiotic (fructo-oligosaccharide, FOS).

Examining the Effects of an Anti-Salmonella Bacteriophage Preparation, BAFASAL, on Ex-Vivo Human Gut Microbiome Composition and Function Using a Multi-Omics Approach.

infections (salmonellosis) pose serious health risks to humans, usually via food-chain contamination. This foodborne pathogen causes major food losses and human illnesses, with significant economic impacts. Overuse of antibiotics in the food industry has led to multidrug-resistant strains of bacteria, and governments are now restricting their use, leading the food industry to search for alternatives to secure food chains.

Exploring the Microbiome-Wide Lysine Acetylation, Succinylation, and Propionylation in Human Gut Microbiota.

Lysine acylations are important post-translational modifications that are present in both eukaryotes and prokaryotes and regulate diverse cellular functions. Our knowledge of the microbiome lysine acylation remains limited due to the lack of efficient analytical and bioinformatics methods for complex microbial communities. Here, we show that the serial enrichment using motif antibodies successfully captures peptides containing lysine acetylation, propionylation, and succinylation from human gut microbiome samples.

Human Skin Gloss Perception Based on Texture Statistics.

We propose objective, image-based techniques for quantitative evaluation of facial skin gloss that is consistent with human judgments. We use polarization photography to obtain separate images of surface and subsurface reflections, and rely on psychophysical studies to uncover and separate the influence of the two components on skin gloss perception. We capture images of facial skin at two levels, macro-scale (whole face) and meso-scale (skin patch), before and after cleansing.

Catching a resurgence: Increase in SARS-CoV-2 viral RNA identified in wastewater 48 h before COVID-19 clinical tests and 96 h before hospitalizations.

Curtailing the Spring 2020 COVID-19 surge required sweeping and stringent interventions by governments across the world. Wastewater-based COVID-19 epidemiology programs have been initiated in many countries to provide public health agencies with a complementary disease tracking metric and non-discriminating surveillance tool. However, their efficacy in prospectively capturing resurgences following a period of low prevalence is unclear.

Optimizing Inpatient Blood Utilization Using Real-Time Clinical Decision Support.

Background: Red blood cell (RBC) transfusion is a common medical procedure. While it offers clinical benefits for many, hemodynamically stable patients are often subjected to unwarranted transfusions, with the potential to lead to adverse consequences. We created a real-time clinical decision support (CDS) tool in the electronic health record system to address this problem and optimize transfusion practice as part of an institutional multidisciplinary, team-based patient blood management program.