A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

The metabolome 18 years on: a concept comes of age

Background

The term ‘metabolome’ was introduced to the scientific literature in September 1998.

Aim and key scientific concepts of the review

To mark its 18-year-old ‘coming of age’, two of the co-authors of that paper review the genesis of metabolomics, whence it has come and where it may be going.

     

Serum metabolomic markers for traumatic brain injury: a mouse model

Introduction

Traumatic brain injury (TBI) is physical injury to brain tissue that temporarily or permanently impairs brain function.

Objectives

Evaluate the use of metabolomics for the development of biomarkers of TBI for the diagnosis and timing of injury onset.

Methods

A validated model of closed injury TBI was employed using 10 TBI mice and 8 sham operated controls. Quantitative LC–MS/MS metabolomic analysis was performed on the serum.

Results

Thirty-six (24.0 %) of 150 metabolites were altered with TBI. Principal component analysis (PCA) and Partial least squares discriminant analysis (PLS-DA) analyses revealed clear segregation between TBI versus control sera. The combination of methionine sulfoxide and the lipid PC aa C34:4 accurately diagnosed TBI, AUC (95 % CI) 0.85 (0.644–1.0). A combination of metabolite markers were highly accurate in distinguishing early (4 h post TBI) from late (24 h) TBI: AUC (95 % CI) 1.0 (1.0–1.0). Spermidine, which is known to have an antioxidant effect and which is known to be metabolically disrupted in TBI, was the most discriminating biomarker based on the variable importance ranking in projection (VIP) plot. Several important metabolic pathways were found to be disrupted including: pathways for arginine, proline, glutathione, cysteine, and sphingolipid metabolism.

Conclusion

Using serum metabolomic analysis we were able to identify novel putative serum biomarkers of TBI. They were accurate for detecting and determining the timing of TBI. In addition, pathway analysis provided important insights into the biochemical mechanisms of brain injury. Potential clinical implications for diagnosis, timing, and monitoring brain injury are discussed.

     

Appropriate use criteria for optical coherence tomography guidance in percutaneous coronary interventions

Introduction

Optical coherence tomography (OCT) enables detailed imaging of the coronary wall, lumen and intracoronary implanted devices. Responding to the lack of specific appropriate use criteria (AUC) for this technique, we conducted a literature review and a procedure for appropriate use criteria.

Methods

Twenty-one of all 184 members of the Dutch Working Group on Interventional Cardiology agreed to evaluate 49 pre-specified cases. During a meeting, factual indications were established whereupon members individually rated indications on a 9-point scale, with the opportunity to substantiate their scoring.

Results

Twenty-six indications were rated ‘Appropriate’, eighteen indications ‘May be appropriate’, and five ‘Rarely appropriate’. Use of OCT was unanimously considered ‘Appropriate’ in stent thrombosis, and ‘Appropriate’ for guidance in PCI, especially in distal left main coronary artery and proximal left anterior descending coronary artery, unexplained angiographic abnormalities, and use of bioresorbable vascular scaffold (BVS). OCT was considered ‘Rarely Appropriate’ on top of fractional flow reserve (FFR) for treatment indication, assessment of strut coverage, bypass anastomoses or assessment of proximal left main coronary artery.

Conclusions

The use of OCT in stent thrombosis is unanimously considered ‘Appropriate’ by these experts. Varying degrees of consensus exists on the appropriate use of OCT in other settings.

     

A Python library for FAIRer access and deposition to the Metabolomics Workbench Data Repository

Introduction

The Metabolomics Workbench Data Repository is a public repository of mass spectrometry and nuclear magnetic resonance data and metadata derived from a wide variety of metabolomics studies. The data and metadata for each study is deposited, stored, and accessed via files in the domain-specific ‘mwTab’ flat file format.

Objectives

In order to improve the accessibility, reusability, and interoperability of the data and metadata stored in ‘mwTab’ formatted files, we implemented a Python library and package. This Python package, named ‘mwtab’, is a parser for the domain-specific ‘mwTab’ flat file format, which provides facilities for reading, accessing, and writing ‘mwTab’ formatted files. Furthermore, the package provides facilities to validate both the format and required metadata elements of a given ‘mwTab’ formatted file.

Methods

In order to develop the ‘mwtab’ package we used the official ‘mwTab’ format specification. We used Git version control along with Python unit-testing framework as well as continuous integration service to run those tests on multiple versions of Python. Package documentation was developed using sphinx documentation generator.

Results

The ‘mwtab’ package provides both Python programmatic library interfaces and command-line interfaces for reading, writing, and validating ‘mwTab’ formatted files. Data and associated metadata are stored within Python dictionary- and list-based data structures, enabling straightforward, ‘pythonic’ access and manipulation of data and metadata. Also, the package provides facilities to convert ‘mwTab’ files into a JSON formatted equivalent, enabling easy reusability of the data by all modern programming languages that implement JSON parsers. The ‘mwtab’ package implements its metadata validation functionality based on a pre-defined JSON schema that can be easily specialized for specific types of metabolomics studies. The library also provides a command-line interface for interconversion between ‘mwTab’ and JSONized formats in raw text and a variety of compressed binary file formats.

Conclusions

The ‘mwtab’ package is an easy-to-use Python package that provides FAIRer utilization of the Metabolomics Workbench Data Repository. The source code is freely available on GitHub and via the Python Package Index. Documentation includes a ‘User Guide’, ‘Tutorial’, and ‘API Reference’. The GitHub repository also provides ‘mwtab’ package unit-tests via a continuous integration service.

     

Fysieke fixatie en slimme technologie in Vlaamse woonzorgcentra: Resultaten van een surveybevraging bij zorg- en beleidspersoneel over visie en gebruik

Aim

The STAFF-project investigates in what way ‘smart technology’ can offer an alternative for physical restraints in nursing homes. A survey is realized aimed at gaining more insight into the vision on and the use of physical restraints and ‘smart technology’.

Method

Two partly overlapping structured questionnaires were developed and sent to nursing home staff in Flanders (Belgium). One hundred fifty six administrators (managers or assistant-managers) and 238 caregiving staff (nurses, nursing aids, paramedical staff and other) completed the online questionnaire.

Results

In general there is a low acceptability of physical restraint use, however, a more nuanced picture of acceptability is present depending on the specific motivation for using physical restraints and on the specific means of physical restraints. About half of the administrators say they use smart technology in the nursing home. The two main reasons for not applying (yet) smart technology are ‘too high price for smart technology’ and ‘inadequate infrastructure of the nursing home’. All respondents underscore the importance of multiple strategies to diminish the use of physical restraints in nursing homes.

Conclusion

Physical restraint use is a complex theme and needs a nuanced analysis and management. This study shows that there is still room for improvement in diminishing the use of physical restraints and that nursing homes in Flanders are open to use smart technology.

     

A systematic review of metabolomics biomarkers for Bisphenol A exposure

Introduction

Bisphenol A (BPA), 2,2-bis(4-hydroxyphenyl) propane, a common industrial chemical which has extremely huge production worldwide, is ubiquitous in the environment. Human have high risk of exposing to BPA and the health problems caused by BPA exposure have aroused public concern. However, the biomarkers for BPA exposure are lacking. As a rapidly developing subject, metabolomics has accumulated a large amount of valuable data in various fields. The secondary application of published metabolomics data could be a very promising field for generating novel biomarkers whilst further understanding of toxicity mechanisms.

Objectives

To summarize the published literature on the use of metabolomics as a tool to study BPA exposure and provide a systematic perspectives of current research on biomarkers screening of BPA exposure.

Methods

We conducted a systematic search of MEDLINE (PubMed) up to the end of June 25, 2017 with the key term combinations of ‘metabolomics’, ‘metabonomics’, ‘mass spectrometry’, ‘nuclear magnetic spectroscopy’, ‘metabolic profiling’ and ‘amino acid profile’ combined with ‘BPA exposure’. Additional articles were identified through searching the reference lists from included studies.

Results

This systematic review included 15 articles. Intermediates of glycolysis, Krebs cycle, β oxidation of long chain fatty acids, pentose phosphate pathway, nucleoside metabolism, branched chain amino acid metabolism, aromatic amino acids metabolism, sulfur-containing amino acids metabolism were significantly changed after BPA exposure, suggesting BPA had a highly complex toxic effects on organism which was consistent with existing studies. The biomarkers most consistently associated with BPA exposure were lactate and choline.

Conclusion

Existing metabolomics studies of BPA exposure present heterogeneous findings regarding metabolite profile characteristics. We need more evidence from target metabolomics and epidemiological studies to further examine the reliability of these biomarkers which link to low, environmentally relevant, exposure of BPA in human body.

     

Advantages of Amplifluor-like SNP markers over KASP in plant genotyping

Background

KASP (KBioscience Competitive Allele Specific PCR) and Amplifluor (Amplification with fluorescence) SNP markers are two prominent technologies based upon a shared identical Allele-specific PCR platform.

Methods

Amplifluor-like SNP and KASP analysis was carried out using published and own design of Universal probes (UPs) and Gene-specific primers (GSPs).

Results

Advantages of the Amplifluor-like system over KASP include the significantly lower costs and much greater flexibility in the adjustment and development of ‘self-designed’ dual fluorescently-labelled UPs and regular GSPs. The presented results include optimisation of ‘tail’ length in UPs and GSPs, protocol adjustment, and the use of various fluorophores in different qPCR instruments. The compatibility of the KASP Master-mix in both original and Amplifluor-like systems has been demonstrated in the presented results, proving their similar principles. Results of SNP scoring with rare alleles in addition to more frequently occurring alleles are shown.

Conclusions

The Amplifluor-like system produces SNP genotyping results with a level of sensitivity and accuracy comparable to KASP but at a significantly cheaper cost and with much greater flexibility for UPs with self-designed GSPs.

     

Quantitative analysis of tetrahydrofolate metabolites from <Emphasis Type="Italic">clostridium autoethanogenum</Emphasis>

Introduction

Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.

Objective

To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.

Methods

Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.

Results

Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.

Conclusion

Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.

     

Timing of simulated aboveground herbivory influences population dynamics of root-feeding nematodes

Aims

A soil-plant-atmosphere continuum (SPAC) model for simulating tree transpiration (Ep) with variable water stress and water distribution in the soil is presented. The model couples a sun/shade approach for the canopy with a discrete representation of the soil in different layers and compartments.

Methods

To test its performance, the outputs from the simulations are compared to those from an experiment using trees of olive ‘Picual’ and almond ‘Marinada’ with the root system split into two. Trees are subjected to different irrigation phases in which one side of the root system is dried out while the other is kept wet.

Results

The model is able to accurately predict Ep (R² and the efficiency factor (EF) around 0.9) in the two species studied. The use of a function that modulates the uptake capacity of a root according to the soil water content was necessary to track the fluxes observed from each split part. It was also appropriate to account for root clumping to match the measured and modelled leaf water potential.

Conclusions

Coupling the sun/shade approach with the soil multi-compartment solution provides a useful tool to explore tree Ep for different degrees of water availability and distribution.

     

Untargeted metabolomics suffers from incomplete raw data processing

Introduction

Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.

Objectives

Assessment of the quality of raw data processing in untargeted metabolomics.

Methods

Five published untargeted metabolomics studies, were reanalyzed.

Results

Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.

Conclusion

Incomplete raw data processing shows unexplored potential of current and legacy data.

     

Growth hormone exacerbates diabetic renal damage in male but not female rats

Background

Human and animal studies support the idea that there are sex differences in the development of diabetic renal disease. Our lab and others have determined that in addition to Ang II (through the AT₁R), growth hormone (GH) contributes to renal damage in models of renal failure; however, the impact of sex and GH on the mechanisms initiating diabetic renal disease is not known. This study examined the effect of sex and GH on parameters of renal damage in early, uncontrolled streptozotocin (STZ)-induced diabetes.

Methods

Adult male and female Sprague–Dawley rats were injected with vehicle (control), STZ, or STZ?+?GH and euthanized after 8 weeks.

Results

Mild but significant glomerulosclerosis (GS) and tubulointerstitial fibrosis (TIF) was observed in both kidneys from male and female diabetic rats, with GH significantly increasing GS and TIF by 30% and 25% in male rats, but not in female rats. STZ increased TGF-β expression in both kidneys from male and female rats; however, while GH had no further effect on TGF-β protein in diabetic females, GH increased TGF-β protein in the male rat’s kidneys by an additional 30%. This sex-specific increase in renal injury following GH treatment was marked by increased MCP-1 and CD-68+ cell density. STZ also reduced renal MMP-2 and MMP-9 protein expression in both kidneys from male and female rats, but additional decreases were only observed in GH-treated diabetic male rats. The sex differences were independent of AT₁R activity.

Conclusions

These studies indicate that GH affects renal injury in diabetes in a sex-specific manner and is associated with an increase in pro-inflammatory mediators.

     

Open versus closed vitrification system of human oocytes and embryos: a systematic review and meta-analysis of embryologic and clinical outcomes

Background

The objective of this study was to carry out a systematic review and meta-analysis of embryologic and clinical outcomes following open versus closed vitrification of human oocytes and embryos.

Methods

An electronic literature search was conducted in main electronic databases up to June 30, 2018 using the following key terms: ‘oocyte’, ‘embryo’, ‘blastocyst’, ‘vitrification’, ‘cryopreservation’, ‘device’, ‘survival rate’, ‘pregnancy rate’, etc. A meta-analysis was performed using a random effect model to estimate the value of risk ratios (RRs) and 95% confidence interval (CI). Subgroup analyses and sensitivity analyses were carried out to further confirm the results.

Results

Twelve (Eight prospective and four retrospective) studies comparing open versus closed vitrification of human oocytes or embryos were included. For prospective studies on oocytes, no evidence for a significant difference in cryosurvival rate (RR?=?0.91, 95% CI: 0.80–1.03, P?=?0.14; n?=?2048) or clinical pregnancy rate (RR?=?1.29, 95% CI: 0.80–2.06, P?=?0.30; n?=?150) was observed. Additionally, there were no significant differences between the two methods concerning secondary endpoints included positive βHCG rate, implantation rate, miscarriage rate, ongoing pregnancy rate, live birth rate, cancellation rate, babies born per transferred blastocysts, or multiple birth rate (P?>?0.05). The results of the retrospective studies were similar as the prospective studies.

Conclusions

It is still impossible to conclude that closed vitrification system could be a substitution for open system in human oocyte and embryo cryopreservation based on current evidence. Therefore, more well-designed prospective studies addressing these issues are still warranted.

     

Metabolic response of porcine colon explants to in vitro infection by <Emphasis Type="Italic">Brachyspira hyodysenteriae</Emphasis>: a leap into disease pathophysiology

Introduction

Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available.

Objective

The aim of this study was to characterize the metabolic response of porcine colon explants to infection by B. hyodysenteriae.

Methods

Porcine colon explants exposed to B. hyodysenteriae were analyzed for histopathological, metabolic and pro-inflammatory gene expression changes.

Results

Significant epithelial necrosis, increased levels of l-citrulline and IL-1α were observed on explants infected with B. hyodysenteriae.

Conclusions

The spirochete induces necrosis in vitro likely through an inflammatory process mediated by IL-1α and NO.

     

Estimating the global warming emissions of the LCAXVII conference: connecting flights matter

Purpose

Conferences are an important element of scientific activity but can also be a major cause of environmental burden. With this in mind, we analysed the global warming emissions of the 2017 annual conference of the American Center for Life Cycle Assessment (ACLCA), in order to estimate the carbon footprint and identify potential ways to reduce it.

Methods

We used survey data from participants as well as literature sources to complete an attributional assessment of the greenhouse gas emissions per participant. A method to calculate the ‘ideal’ location is proposed, which can be used to identify ‘unreasonably’ distant conference locations.

Results and discussion

The average emissions per participant were found to be 952 kg CO_2eq, but with a large variability due to differences in travelled distance. Connecting flights were found to increase emissions up to 32% compared to direct flights, due to the increased number of take-offs and landings.

Conclusions

Results indicate that future studies should use distance-dependent flight emissions to increase the accuracy of the assessment. Some measures, such as meat-free menus, had a relatively minor contribution to emission reductions, but could be important as scientists advocating for the reduction of environmental burden should lead by example.

     

Comparison if the addition of multilevel vertebral augmentation to conventional therapy will improve the outcome of patients with multiple myeloma

Background

This was a prospective study to evaluate the effect of multilevel vertebral augmentation in addition to conventional therapy in multiple myeloma patients.

Methods

We treated 27 patients, whom were recently diagnosed to have multiple myeloma by two ways of treatment. Thirteen patients (group I) were treated with conventional therapy and 14 patients (group II) with adding vertebroplasty and kyphoplasty. Patients were evaluated pre-treatment and at half, one, two and 3-years post-treatment by using Oswestry Disability Index (ODI), the Stanford Score (SS) and the Spinal Instability Neoplastic Score (SINS).

Results

Mean values of ODI, SS and SINS were 31.9 (63.8%), 4.3 and 13.8 for group I and 33.2 (66.4%), 4.6 and 12.8 for group II before starting treatment. Group II showed improvement better than group I at all follow-up intervals with best results at first 6 months. P-values at the end of the study were ODI?=?0.047, SS?=?0.180 and SINS?=?0.002. Mortality rates were equal of both groups (four patients of each group).

Conclusion

Adding vertebral augmentation to conventional therapy improves multiple myeloma patients’ quality of life, but didn’t affect the mortality rate.

     

Early recognition of sudden cardiac arrest in athletes during sports activity

Introduction

Sudden cardiac arrest (SCA) in athletes is an unexpected life-threatening event, which is often not recognised early and cardiopulmonary resuscitation (CPR) is not always initiated immediately. We describe key features to rapidly recognise non-traumatic SCA in athletes during sports activity.

Methods

We reviewed videos and images of athletes suffering from non-traumatic SCA during sports activity. We searched Google images, Google videos and YouTube.com using the keywords ‘sudden cardiac death athlete’ and ‘resuscitation athlete’. We analysed (1) the athlete’s performance before syncope, (2) the athlete’s performance at the start of syncope, (3) the position of the body, and (4) the athlete’s facial expressions before CPR. We analysed our data by describing these four features to answer our research question.

Results

We analysed the sequence of events in six well-known soccer players in whom a camera-witnessed non-traumatic SCA occurred during their athletic activity. All six athletes showed no changes before syncope. Four became unstable while standing and unexpectedly collapsed falling on their back. Two suddenly ‘dropped dead’ and fell face down. All six had their eyes wide open with a fixed gaze and fixed pupils.

Conclusions

Sudden unexpected loss of consciousness in an athlete in action and a fixed gaze eye position are key features of SCA. Immediate cardiac massage should follow. The described features to immediately recognise SCA in athletes during sports activity should be taught to everyone involved in athletic activity leading to earlier recognition of SCA followed by earlier CPR.

     

Pharmacokinetics of recombinant human growth hormone administered by cool.click™ 2, a new needle-free device,compared with subcutaneous administration using a conventional syringe and needle

Background

Growth hormone (GH) is used to treat growth hormone deficiency (GHD, adult and paediatric), short bowel syndrome in patients on a specialized diet, HIV-associated wasting and, in children, growth failure due to a number of disorders including Turner's syndrome and chronic renal failure, and in children born small for gestational age. Different brands and generic forms of recombinant human growth hormone (r-hGH) are approved for varying indications in different countries. New ways of administering GH are required because the use of a needle and syringe or a device where a patient still has to insert the needle manually into the skin on a daily basis can lead to low adherence and sub-optimal treatment outcomes. The objective of this study was to assess the relative bioavailability of r-hGH (Saizen^®, Merck Serono) administered by a new needle-free device, cool.click? 2, and a standard needle and syringe.

Methods

The study was performed with 38 healthy volunteers who underwent pituitary somatotrope cell down-regulation using somatostatin, according to a randomized, two-period, two-sequence crossover design. Following subcutaneous administration of r-hGH using cool.click? 2 or needle and syringe, pharmacokinetic parameters were analysed by non-compartmental methods. Bioequivalence was assessed based on log-transformed AUC and C_max values.

Results

The 90% confidence intervals for test/reference mean ratio of the plasma pharmacokinetic variables C_max and AUC_0-inf were 103.7–118.3 and 97.1–110.0, respectively, which is within the accepted bioequivalence range of 80–125%. r-hGH administered by cool.click? 2 is, therefore, bioequivalent to administration by needle and syringe with respect to the rate and extent of GH exposure. Treatment using cool.click? 2 was found to be well tolerated. With cool.click? 2 the t_max was less (3.0 hours) than for needle and syringe delivery (4.5 hours), p = 0.002 (Friedman test), although this is unlikely to have any clinical implications.

Conclusion

These results demonstrate that cool.click? 2 delivers subcutaneous r-hGH exposure that is bioequivalent to the conventional mode of injection. The new device has the additional advantage of being needle-free, and should help to increase patient adherence and achieve good therapeutic outcomes from r-hGH treatment.