Bioinformatic approaches for studying the microbiome of fermented food

peer-reviewedHigh-throughput DNA sequencing-based approaches continue to revolutionise our understanding of microbial ecosystems, including those associated with fermented foods. Metagenomic and metatranscriptomic approaches are state-of-the-art biological profiling methods and are employed to investigate a wide variety of characteristics of microbial communities, such as taxonomic membership, gene content and the range and level at which these genes are expressed. Individual groups and consortia of researchers are utilising these approaches to produce increasingly large and complex datasets, representing vast populations of microorganisms. There is a corresponding requirement for the development and application of appropriate bioinformatic tools and pipelines to interpret this data. This review critically analyses the tools and pipelines that have been used or that could be applied to the analysis of metagenomic and metatranscriptomic data from fermented foods. In addition, we critically analyse a number of studies of fermented foods in which these tools have previously been applied, to highlight the insights that these approaches can provide.European Union’s Horizon 2020 research and innovation programm

Analysis of the Milk Kefir Pan-Metagenome Reveals Four Community Types, Core Species and Associated Metabolic Pathways

peer-reviewedA comprehensive metagenomics-based investigation of the microorganisms present within milk kefir communities from across the globe was carried out with a view to defining the milk kefir pan-metagenome, including details relating to core and non-core components. Milk kefir samples, generated by inoculating full fat, pasteurized cow’s milk with 64 kefir grains sourced from 25 different countries, were analyzed. We identified core features, including a consistent pattern of domination by representatives from the species Lactobacillus helveticus or the sub-species Lactobacillus kefiranofaciens subsp. kefiranofaciens, Lactococcus lactis subsp. lactis or Lla. cremoris subsp. cremoris in each kefir. Notably, even in kefirs where the lactococci did not dominate, they and 51 associated metabolic pathways were identified across all metagenomes. These insights can contribute to future efforts to create tailored kefir-based microbial communities for different applications and assist regulators and producers to ensure that kefir products have a microbial composition that reflects the artisanal beverage

Kefir4All, a citizen science initiative to raise awareness of the roles that microbes play in food fermentation

peer-reviewedMicroorganisms are ubiquitous in nature and are central to human, animal, environmental, and planetary health. They play a particularly important role in the food chain and the production of high-quality, safe, and health-promoting foods, especially fermented foods. This important role is not always apparent to members of the public. Here, we describe Kefir4All, a citizen science project designed to provide the general public with an opportunity to expand their awareness, knowledge, and practical skills relating to microbiology, introduced through the medium of producing fermented food, i.e., milk kefir or water kefir. During the course of Kefir4All, 123 citizen scientists, from second-level school and non-school settings, participated in a study to track changes in the microbial composition of kefirs, by performing and recording details of milk kefir or water kefir fermentations they performed in their homes or schools over the 21-week project. At the start of the study, the citizen scientists were provided with milk or water kefir grains to initiate the fermentations. Both types of kefir grain are semi-solid, gelatinous-like substances, composed of exopolysaccharides and proteins, containing a symbiotic community of bacteria and yeast. The experimental component of the project was complemented by a number of education and outreach events, including career talks and a site visit to our research center (Kefir Day). At the end of the study, a report was provided to each citizen scientist, in which individualized results of their fermenting activities were detailed. A number of approaches were taken to obtain feedback and other insights from the citizen scientists. Evaluations took place before and after the Kefir4All project to gauge the citizen scientist’s self-reported awareness, knowledge, and interest in microbiology and fermented foods. Further insights into the level of citizen science participation were gained through assessing the number of samples returned for analysis and the level of participation of the citizen scientists throughout the project. Notably, the survey results revealed a self-reported, increased interest in, and general knowledge of, science among the Kefir4All citizen scientists after undertaking the project and a willingness to take part in further citizen science projects. Ultimately, Kefir4All represents an example of the successful integration of citizen science into existing education and research systems

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV

The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe