Microbiome and Metabolome Restoration After Administration of Fecal Microbiota, Live-jslm (REBYOTA®) for Preventing Recurrent Clostridioides difficile Infection.

Background: Microbiota-based treatments are effective in preventing recurrent Clostridioides difficile infection (rCDI). Fecal microbiota, live-jslm (REBYOTA®; RBL, previously RBX2660) was shown to prevent rCDI in a phase 3, randomized, double-blinded placebo controlled clinical trial (PUNCH™ CD3).

Methods: Stool samples from participants in PUNCH™ CD3 who received a single blinded dose of rectally administered RBL or placebo were sequenced to determine microbial community composition and calculate the Microbiome Health Index for post-antibiotic dysbiosis (MHI-A).

Towards the Simplest Model of Quantum Supremacy: Atomic Boson Sampling in a Box Trap.

We describe boson sampling of interacting atoms from the noncondensed fraction of Bose-Einstein-condensed (BEC) gas confined in a box trap as a new platform for studying computational ♯P-hardness and quantum supremacy of many-body systems. We calculate the characteristic function and statistics of atom numbers via the newly found Hafnian master theorem. Using Bloch-Messiah reduction, we find that interatomic interactions give rise to two equally important entities-eigen-squeeze modes and eigen-energy quasiparticles-whose interplay with sampling atom states determines the behavior of the BEC gas.

Human Fecal Bile Acid Analysis after Investigational Microbiota-Based Live Biotherapeutic Delivery for Recurrent Infection.

Microbiome-based therapeutics are increasingly evaluated as a strategy to reduce recurrent infection (rCDI), with proposed mechanisms including restoration of the microbiota and microbiota-mediated functions, such as bile acid (BA) metabolism. This study reports a quantitative and sensitive assay for targeted metabolomic assessment, and the application of the assay to profile BA composition in a Phase 2 trial of the investigational microbiota-based live biotherapeutic RBX2660 for reduction of rCDI. A liquid chromatography tandem mass spectrometry method was developed to extract and quantify 35 BAs from 113 participant stool samples from 27 RBX2660-treated rCDI participants in the double-blinded, placebo-controlled clinical trial.

Multi-Qubit Bose-Einstein Condensate Trap for Atomic Boson Sampling.

We propose a multi-qubit Bose-Einstein-condensate (BEC) trap as a platform for studies of quantum statistical phenomena in many-body interacting systems. In particular, it could facilitate testing atomic boson sampling of the excited-state occupations and its quantum advantage over classical computing in a full, controllable and clear way. Contrary to a linear interferometer enabling Gaussian boson sampling of non-interacting non-equilibrium photons, the BEC trap platform pertains to an interacting equilibrium many-body system of atoms.

Development and Validation of a Novel Microbiome-Based Biomarker of Post-antibiotic Dysbiosis and Subsequent Restoration.

The human gut microbiota are important to health and wellness, and disrupted microbiota homeostasis, or "dysbiosis," can cause or contribute to many gastrointestinal disease states. Dysbiosis can be caused by many factors, most notably antibiotic treatment. To correct dysbiosis and restore healthier microbiota, several investigational microbiota-based live biotherapeutic products (LBPs) are in formal clinical development.

Soil Buffering Capacity Can Be Used To Optimize Biostimulation of Psychrotrophic Hydrocarbon Remediation.

Effective bioremediation of hydrocarbons requires innovative approaches to minimize phosphate precipitation in soils of different buffering capacities. Understanding the mechanisms underlying sustained stimulation of bacterial activity remains a key challenge for optimizing bioremediation-particularly in northern regions. Positron emission tomography (PET) can trace microbial activity within the naturally occurring soil structure of intact soils.

DiPODS: A Reagent for Site-Specific Bioconjugation via the Irreversible Rebridging of Disulfide Linkages.

Chemoselective reactions with thiols have long held promise for the site-specific bioconjugation of antibodies and antibody fragments. Yet bifunctional probes bearing monovalent maleimides-long the "gold standard" for thiol-based ligations-are hampered by two intrinsic issues: the instability of the maleimide-thiol bond and the need to permanently disrupt disulfide linkages in order to facilitate bioconjugation. Herein, we present the synthesis, characterization, and validation of DiPODS, a novel bioconjugation reagent containing a pair of oxadiazolyl methyl sulfone moieties capable of irreversibly forming covalent bonds with two thiolate groups while simultaneously rebridging disulfide linkages.

RBX7455, a Non-frozen, Orally Administered Investigational Live Biotherapeutic, Is Safe, Effective, and Shifts Patients' Microbiomes in a Phase 1 Study for Recurrent Clostridioides difficile Infections.

Background: Recurrent Clostridioides difficile infections (rCDI) are a global public health threat. To reduce rCDI, microbiota-restoring therapies are needed, particularly standardized, easy-to-administer formulations.

Methods: This phase I open-label trial assessed the safety, efficacy in preventing rCDI recurrence, and intestinal microbiome effects of RBX7455, a room temperature-stable, orally administered investigational live biotherapeutic.

Revisiting the Radiosynthesis of [F]FPEB and Preliminary PET Imaging in a Mouse Model of Alzheimer's Disease.

[F]FPEB is a positron emission tomography (PET) radiopharmaceutical used for imaging the abundance and distribution of mGluR5 in the central nervous system (CNS). Efficient radiolabeling of the aromatic ring of [F]FPEB has been an ongoing challenge. Herein, five metal-free precursors for the radiofluorination of [F]FPEB were compared, namely, a chloro-, nitro-, sulfonium salt, and two spirocyclic iodonium ylide (SCIDY) precursors bearing a cyclopentyl (SPI5) and a new adamantyl (SPIAd) auxiliary.

New statistical method identifies cytokines that distinguish stool microbiomes.

Regressing an outcome or dependent variable onto a set of input or independent variables allows the analyst to measure associations between the two so that changes in the outcome can be described by and predicted by changes in the inputs. While there are many ways of doing this in classical statistics, where the dependent variable has certain properties (e.g.

Little Change in Functional Brain Networks Following Acute Levodopa in Drug-Naïve Parkinson's Disease.

Objective: The objective of this study was to investigate the effects of levodopa on functional brain networks in Parkinson's disease.

Methods: We acquired resting state functional magnetic resonance imaging in 30 drug-naïve participants with Parkinson's disease and 20 age-matched healthy controls. Each participant was studied following administration of a single oral dose of either levodopa or placebo in a randomized, double-blind, crossover design.

Detecting associations between intact connectomes and clinical covariates using recursive partitioning object-oriented data analysis.

Many neuroscientists are interested in how connectomes (graphical representations of functional connectivity between areas of the brain) change in relation to covariates. In statistics, changes like this are analyzed using regression, where the outcomes or dependent variables are regressed onto the covariates. However, when the outcome is a complex object, such as connectome graphs, classical regression models cannot be used.

Restoration of Bacterial Microbiome Composition and Diversity Among Treatment Responders in a Phase 2 Trial of RBX2660: An Investigational Microbiome Restoration Therapeutic.

Background: RBX2660 is an investigational microbiota restoration therapy in phase 3 clinical development for preventing recurrent infections (CDIs). In a randomized, double-blinded placebo-controlled phase 2B trial, RBX2660 was effective at preventing CDI recurrence. The current study was performed to characterize the fecal bacterial microbiome before and after treatment among RBX2660- or placebo-treated responders in that trial.

Emergent Functional Network Effects in Parkinson Disease.

The hallmark pathology underlying Parkinson disease (PD) is progressive synucleinopathy, beginning in caudal brainstem that later spreads rostrally. However, the primarily subcortical pathology fails to account for the wide spectrum of clinical manifestations in PD. To reconcile these observations, resting-state functional connectivity (FC) can be used to examine dysfunction across distributed brain networks.

Independence of gut bacterial content and neonatal necrotizing enterocolitis severity.

Introduction: Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal disease of premature infants. NEC severity varies widely. Recent data have demonstrated a strong link between gut microbial dysbiosis and development of NEC.

Mobilization of allogeneic peripheral blood stem cell donors with intravenous plerixafor mobilizes a unique graft.

A single subcutaneous (SC) injection of plerixafor results in rapid mobilization of hematopoietic progenitors, but fails to mobilize 33% of normal allogeneic sibling donors in 1 apheresis. We hypothesized that changing the route of administration of plerixafor from SC to IV may overcome the low stem cell yields and allow collection in 1 day. A phase 1 trial followed by a phase 2 efficacy trial was conducted in allogeneic sibling donors.

Pharmacokinetics and analgesic effects of methadone in children and adults with sickle cell disease.

Background: Vaso-occlusive episodes (VOEs) are a significant source of morbidity among children and adults with sickle cell disease (SCD). There is little information on methadone use for SCD pain. This investigation evaluated methadone pharmacokinetics in children and adults with SCD, with a secondary aim to assess pain relief and opioid consumption.

Topical Decolonization Does Not Eradicate the Skin Microbiota of Community-Dwelling or Hospitalized Adults.

Topical antimicrobials are often employed for decolonization and infection prevention and may alter the endogenous microbiota of the skin. The objective of this study was to compare the microbial communities and levels of richness and diversity in community-dwelling subjects and intensive care unit (ICU) patients before and after the use of topical decolonization protocols. We enrolled 15 adults at risk for Staphylococcus aureus infection.

Daily global stress is associated with nocturnal asthma awakenings in school-age children.

Greater child daily global stress was associated with increased likelihood of awakening from asthma that night. Asthma awakenings were followed by greater morbidity the next day.

A web application for sample size and power calculation in case-control microbiome studies.

Unlabelled: : When designing a case-control study to investigate differences in microbial composition, it is fundamental to assess the sample sizes needed to detect an hypothesized difference with sufficient statistical power. Our application includes power calculation for (i) a recoded version of the two-sample generalized Wald test of the 'HMP' R-package for comparing community composition, and (ii) the Wilcoxon-Mann-Whitney test for comparing operational taxonomic unit-specific abundances between two samples (optional). The simulation-based power calculations make use of the Dirichlet-Multinomial model to describe and generate abundances.

Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study.

Background: Gut bacteria might predispose to or protect from necrotising enterocolitis, a severe illness linked to prematurity. In this observational prospective study we aimed to assess whether one or more bacterial taxa in the gut differ between infants who subsequently develop necrotising enterocolitis (cases) and those who do not (controls).

Methods: We enrolled very low birthweight (1500 g and lower) infants in the primary cohort (St Louis Children's Hospital) between July 7, 2009, and Sept 16, 2013, and in the secondary cohorts (Kosair Children's Hospital and Children's Hospital at Oklahoma University) between Sept 12, 2011 and May 25, 2013.

Gibbs distribution for statistical analysis of graphical data with a sample application to fcMRI brain images.

This paper develops object-oriented data analysis (OODA) statistical methods that are novel and complementary to existing methods of analysis of human brain scan connectomes, defined as graphs representing brain anatomical or functional connectivity. OODA is an emerging field where classical statistical approaches (e.g.