Genome-scale human protein-protein interaction networks are critical to understanding cell biology and interpreting genomic data, but challenging to produce experimentally. Through data integration ...and quality control, we provide a scored human protein-protein interaction network (InWeb_InBioMap, or InWeb_IM) with severalfold more interactions (>500,000) and better functional biological relevance than comparable resources. We illustrate that InWeb_InBioMap enables functional interpretation of >4,700 cancer genomes and genes involved in autism.
Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in ...healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.
Globally, food production for an ever-growing population is a well-known threat to the environment due to losses of excess reactive nitrogen (N) from agriculture. Since the 1980s, many countries of ...the Global North, such as Denmark, have successfully combatted N pollution in the aquatic environment by regulation and introduction of national agricultural one-size-fits-all mitigation measures. Despite this success, further reduction of the N load is required to meet the EU water directives demands, and implementation of additional targeted N regulation of agriculture has scientifically and politically been found to be a way forward. In this paper, we present a comprehensive concept to make future targeted N regulation successful environmentally and economically. The concept focus is on how and where to establish detailed maps of the groundwater denitrification potential (N retention) in areas, such as Denmark, covered by Quaternary deposits. Quaternary deposits are abundant in many parts of the world, and often feature very complex geological and geochemical architectures. We show that this subsurface complexity results in large local differences in groundwater N retention. Prioritization of the most complex areas for implementation of the new concept can be a cost-efficient way to achieve lower N impact on the aquatic environment.
Cost-efficient targeted nitrogen (N) regulation of agriculture with low impact on the environment is the new N regulation paradigm. It requires detailed knowledge on the geological and geochemical ...conditions of the subsurface that is crucial for assessing the nitrate flowpaths and reduction processes. An integral part of this is analysis of the subsurface redox structures to determine the locations of nitrate reduction. This knowledge has so far not been easy to access because of lacking technology. Here we present a new concept consisting of integration and interpretation of data from the geophysical towed transient electromagnetic method, borehole information on lithology, sediment colour descriptions, geochemistry and groundwater chemistry. The concept is demonstrated in three small first-order hydrological catchments. National GIS screening analyses show that the new concept is highly needed in large parts of Denmark where the redox structures are complicated e.g. in marine landscape types and in glacial moraine landscapes but less needed in areas dominated by homogeneous meltwater plains. Providing subsurface knowledge for locally targeted N regulation of agriculture is paramount in many developed countries with intensive agriculture to lower the environmental impact, and it could also be critical in developing countries to support sustainable economic and environmental development.
•Food chain workers are exposed to antimicrobial resistant (AMR) bacteria in livestock.•We describe faecal resistomes and microbiomes of farmers and slaughterhouse workers.•Faecal AMR gene loads in ...pork exposed workers exceed those in broiler farmers/controls.•Resistome and microbiome differences are shown between and within occupational groups.•On-farm working hours and working/living on a pig farm determinethe faecal resistome.•Contact with livestock may be a determinant for human AMR gene carriage.
By studying the entire human faecal resistome and associated microbiome, the diversity and abundance of faecal antimicrobial resistance genes (ARGs) can be comprehensively characterized. Prior culture-based studies have shown associations between occupational exposure to livestock and carriage of specific antimicrobial resistant bacteria. Using shotgun metagenomics, the present study investigated 194 faecal resistomes and bacteriomes from humans occupationally exposed to ARGs in livestock (i.e. pig and poultry farmers, employees and family members and pig slaughterhouse workers) and a control population (Lifelines cohort) in the Netherlands. In addition, we sought to identify determinants for the human resistome and bacteriome composition by applying a combination of multivariate (NMDS, PERMANOVA, SIMPER and DESeq2 analysis) and multivariable regression analysis techniques.
Pig slaughterhouse workers and pig farmers carried higher total ARG abundances in their stools compared to broiler farmers and control subjects. Tetracycline, β-lactam and macrolide resistance gene clusters dominated the resistome of all studied groups. No significant resistome alpha diversity differences were found among the four populations. However, the resistome beta diversity showed a separation of the mean resistome composition of pig and pork exposed workers from broiler farmers and controls, independent of their antimicrobial use. We demonstrated differences in resistome composition between slaughter line positions, pig versus poultry exposed workers, as well as differences between farmers and employees versus family members. In addition, we found a significant correlation between the bacteriome and resistome, and significant differences in the bacteriome composition between and within the studied subpopulations. Finally, an in-depth analysis of pig and poultry farms – of which also farm livestock resistomes were analysed – showed positive associations between the number of on-farm working hours and human faecal AMR loads.
We found that the total normalized faecal ARG carriage was larger in persons working in the Dutch pork production chain compared to poultry farmers and controls. Additionally, we showed significant differences in resistome and bacteriome composition of pig and pork exposed workers compared to a control group, as well as within-population (farms, slaughterhouse) compositional differences. The number of on-farm working hours and the farm type (pig or broiler) that persons live or work on are determinants for the human faecal resistome. Overall, our results may suggest direct or indirect livestock contact as a determinant for human ARG carriage. Future studies should further focus on the connection between the human and livestock resistome (i.e. transmission routes) to substantiate the evidence for livestock-associated resistome acquisition.
Abstract
Objectives
Previous studies in food-producing animals have shown associations between antimicrobial use (AMU) and resistance (AMR) in specifically isolated bacterial species. Multi-country ...data are scarce and only describe between-country differences. Here we investigate associations between the pig faecal mobile resistome and characteristics at the farm-level across Europe.
Methods
A cross-sectional study was conducted among 176 conventional pig farms from nine European countries. Twenty-five faecal samples from fattening pigs were pooled per farm and acquired resistomes were determined using shotgun metagenomics and the Resfinder reference database, i.e. the full collection of horizontally acquired AMR genes (ARGs). Normalized fragments resistance genes per kilobase reference per million bacterial fragments (FPKM) were calculated. Specific farm-level data (AMU, biosecurity) were collected. Random-effects meta-analyses were performed by country, relating farm-level data to relative ARG abundances (FPKM).
Results
Total AMU during fattening was positively associated with total ARG (total FPKM). Positive associations were particularly observed between widely used macrolides and tetracyclines, and ARGs corresponding to the respective antimicrobial classes. Significant AMU-ARG associations were not found for β-lactams and only few colistin ARGs were found, despite high use of these antimicrobial classes in younger pigs. Increased internal biosecurity was directly related to higher abundances of ARGs mainly encoding macrolide resistance. These effects of biosecurity were independent of AMU in mutually adjusted models.
Conclusions
Using resistome data in association studies is unprecedented and adds accuracy and new insights to previously observed AMU-AMR associations. Major components of the pig resistome are positively and independently associated with on-farm AMU and biosecurity conditions.
This study evaluated if medical doctors could identify more hemorrhage events during chart review in a clinical setting when assisted by an artificial intelligence (AI) model, and medical doctors' ...perception of using the AI model.
To develop the AI model, sentences from 900 electronic health records were labeled as positive or negative for hemorrhage and categorized into one of twelve anatomical locations. The AI model was evaluated on a test cohort consisting of 566 admissions. Using eye-tracking technology, we investigated medical doctors' reading workflow during manual chart review. Moreover, we performed a clinical use study where medical doctors read two admissions with and without AI assistance to evaluate performance when, and perception of using the AI model.
The AI model had a sensitivity of 93.7% and a specificity of 98.1% on the test cohort. In the use studies, we found that medical doctors missed more than 33% of relevant sentences when doing chart review without AI assistance. Hemorrhage events described in paragraphs were more often overlooked compared to bullet-pointed hemorrhage mentions. With AI assisted chart review, medical doctors identified 48 and 49 percentage points more hemorrhage events than without assistance in two admissions, and they were generally positive towards using the AI model as a supporting tool.
Medical doctors identified more hemorrhage events with AI assisted chart review and they were generally positive towards using the AI model.
The majority of long coronavirus disease (COVID) symptoms are not specific to COVID-19 and could be explained by other conditions. The present study aimed to explore whether Danish individuals with a ...perception that they suffer from long COVID have antibodies against the nucleocapsid antigen, as a proxy for detecting previous infection. The study was conducted in February and March 2021, right after the second surge of the COVID-19 pandemic in Denmark. All members of the social media group on Facebook "Covidramte med senfølger" ("long COVID sufferers'') above the age of 17 years and living in Denmark were invited to participate in a short electronic questionnaire about long COVID risk factors and symptoms. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein was detected in blood samples as a proxy for natural SARS-CoV-2 infection. The final study population comprised 341 participants (90.6% females) who completed blood sampling and answered the questionnaire. A total of 232 (68%) were seropositive (median age, 49.5 years; interquartile range IQR, 41 to 55 years; 90.1% females). There was no significant difference between sexes and serostatus. Seronegative and seropositive individuals had a similar burden of symptoms that could be attributed to long COVID. Time since perceived COVID-19 was significantly longer in the group of seronegative individuals than the seropositive ones (
< 0.001). This study suggests that long-COVID sufferers are mostly women and showed that a third of the participants did not have detectable anti-N-protein antibodies. It emphasizes the importance of early confirmation of COVID-19, as this study indicates an overlap between long-COVID symptoms and symptoms that are possibly of another origin.
This cohort study included questionnaire data as well as anti-nucleocapsid antibody analysis, allowing us to determine whether participants were seropositive due to vaccination or natural infection. The study emphasizes the importance of early confirmation of COVID-19, as antibodies recede with time, and it indicates an overlap between long COVID symptoms and symptoms possibly of another origin.
•Routine biomarkers can accurately predict mortality in acutely admitted patients.•Simple and easily calculated blood test score.•Potential to increase risk stratification when combining blood tests ...with triage.
This study aimed to improve early risk stratification in the emergency department by creating a simple blood test score based on routine biomarkers and assess its predictive ability for 30-day mortality of acutely admitted patients.
This was a secondary analysis of data from the TRIAGE II study. It included unselected acutely admitted medical and surgical patients, who had albumin, C-reactive protein, creatinine, haemoglobin, leukocytes, potassium, sodium and thrombocytes levels analysed upon admission. Patients were classified according to the number of biomarker results outside the reference range into four risk groups termed “very low”, “low”, “intermediate”, and “high” with 0–1, 2–3, 4–5 and 6–8 abnormal biomarker results, respectively. Logistic regression was used to calculate odds ratios for 30-day mortality and receiver operating characteristic was used to test the discriminative value. The primary analysis was done in patients triaged with ADAPT (Adaptive Process Triage). Subsequently, we analysed two other cohorts of acutely admitted patients.
The TRIAGE II cohort included 17,058 eligible patients, 30-day mortality was 5.2%. The primary analysis included 7782 patients. Logistic regression adjusted for age and sex showed an OR of 24.1 (95% CI 14.9–41.0) between the very low- and the high-risk group. The area under the curve (AUC) was 0.79 (95% CI 0.76–0.81) for the blood test score in predicting 30-day mortality. The subsequent analyses confirmed the results.
A blood test score based on number of routine biomarkers with an abnormal result was a predictor of 30-day mortality in acutely admitted patients.
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