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 effect of cognitive appraisal for stressors on the oral health-related QOL of dry mouth patients

Background

Dry mouth is very common symptom, and psychological factors have an influence on this symptom. Although the influence of emotional factor related to patients with oral dryness has been examined in previous studies, the cognitive factors have not been examined thus far.

Objective

The purpose of this study was to examine the influence of cognitive factors on patients with oral dryness.

Methods

The participants were 106 patients complaining of oral dryness. They were required to complete a questionnaire measuring subjective oral dryness, oral-related QOL, cognition for stressors, and mood state.

Results

Correlational analyses revealed that OHIP-14 is significantly related to oral dryness, appraisal for effect, appraisal for threat, and commitment. These correlations were maintained even after controlling for the influence of depression and anxiety. Using oral dryness, appraisal for effect, appraisal for threat, and commitment, cluster analysis was done and three clusters (cluster-1, severe oral dryness; cluster-2, positive cognitive style: cluster-3, negative cognitive style) were extracted. The results of ANOVA showed that the group with severe oral dryness (cluster-1) had a significantly higher score on OHIP-14 than the other two groups. There was no significant difference between the groups with positive (cluster-2) and negative (cluster-3) cognitive style.

Conclusion

Although the group of patients with positive cognitive style complained of more severe oral dryness than the group with negative cognitive style, no significant difference was observed between these two groups in OHIP-14. These results indicate that cognitive factors would be a useful therapeutic target for the improvement of the oral-related QOL of patients with oral dryness.

     

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.

     

KniMet: a pipeline for the processing of chromatography–mass spectrometry metabolomics data

Introduction

Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.

Objectives

Merge in the same platform the steps required for metabolomics data processing.

Methods

KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.

Results

The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.

Conclusion

KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.

     

De relatie tussen apathie,depressie en cognitief functioneren bij patiënten met MCI en dementie

Background

In dementia, apathy and depression are often seen as one disorder because of the many overlapping symptoms. However, for therapy a correct differentiation is essential. Moreover, apathy and depression are likely both associated with different cognitive deficits and progression of the disease. In this research we give an overview of cognitive domains associated with apathy and depression in MCI patients and report how often both disorders occur in a population sample.

Method

We administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to 117 cognitively healthy controls (GC), 97 patients with mild cognitive impairment (MCI) and 50 patients with dementia (DEM). In addition, the Apathy Evaluation Scale clinical version (AES-C) and the Geriatric Depression Scale (GDS) were administered.

Results

The number of patients with apathy increased with cognitive decline with respectively 3.4%, 10.4% and 41.5% of patients in the GC, MCI and DEM group. The prevalence of isolated depression was highest in the MCI group (18.8%). Correlation analyses in the MCI group showed that apathy and not depression was associated with a deficit in encoding, attention and global cognitive functioning.

Conclusion

The prevalence of apathy and depressive symptoms is different in patients with MCI, DEM and GC, and within the MCI group apathy and depression are associated with different cognitive domains.

     

Attention needed for cognitive problems in patients after out-of-hospital cardiac arrest: an inventory about daily rehabilitation care

Aim

Recent literature and Dutch guidelines for patients with out-of-hospital cardiac arrest (OHCA) recommend screening for cognitive impairments and referral to cognitive rehabilitation when needed. The aim of this study is to assess the uptake of these recommendations for OHCA patients.

Method

An internet-based questionnaire was sent to 74 cardiologists and 143 rehabilitation specialists involved in rehabilitation of OHCA patients in the Netherlands. The questionnaire covered: background characteristics, availability and content of cognitive screening and rehabilitation, organisation of care, experienced need for an integrated care pathway including physical and cognitive rehabilitation, barriers and facilitators for an integrated care pathway.

Results

Forty-five questionnaires were returned (16 cardiologists and 29 rehabilitation doctors). Thirty-nine percent (n?=?17) prescribed cognitive screening. Eighty-nine percent underscores an added value of an integrated care pathway. Barriers for an integrated care pathway included lack of knowledge, logistic obstacles, and poor cooperation between medical specialties.

Conclusions

In the Netherlands, only a minority of cardiologists and rehabilitation specialists routinely prescribe some form of cognitive screening in OHCA patients, although the majority underscores the value of cognitive screening in OHCA patients in an integrated care pathway. The uptake of such a care pathway seems hindered by lack of knowledge and organisational barriers.

     

NMRProcFlow: a graphical and interactive tool dedicated to 1D spectra processing for NMR-based metabolomics

Introduction

Concerning NMR-based metabolomics, 1D spectra processing often requires an expert eye for disentangling the intertwined peaks.

Objectives

The objective of NMRProcFlow is to assist the expert in this task in the best way without requirement of programming skills.

Methods

NMRProcFlow was developed to be a graphical and interactive 1D NMR (¹H & ¹³C) spectra processing tool.

Results

NMRProcFlow (http://nmrprocflow.org), dedicated to metabolic fingerprinting and targeted metabolomics, covers all spectra processing steps including baseline correction, chemical shift calibration and alignment.

Conclusion

Biologists and NMR spectroscopists can easily interact and develop synergies by visualizing the NMR spectra along with their corresponding experimental-factor levels, thus setting a bridge between experimental design and subsequent statistical analyses.

     

The Turkish validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery

Background

Cognitive impairment may be seen in as many as 43–70% of patients with multiple sclerosis (MS) and may be observed in all MS subtypes. The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS) battery may be used to evaluate cognition status. The purpose of the current study is to validate the BICAMS battery in Turkish.

Methods

Patients with MS attending our clinic between September 2014 and April 2015 were invited to participate. Healthy control participants were matched in terms of age, gender and years of education.

Results

One hundred seventy-three MS patients and 153 healthy control participants were enrolled in the study. MS patients performed significantly worse in all trials than the members of the healthy control group. In addition, cognitive dysfunction was identified in 78 of the 173 (45.1%) patients. In the MS with cognitive impairment group, 64 out of 151 (42.4%) subjects were RRMS patients, 12 out of 18 (66.7%) were secondary progressive MS patients, and 2 out of 4 (50%) were primer progressive MS patients.

Conclusions

The BICAMS has been proposed for assessing cognitive impairment in MS patients. This study shows that the battery is suitable for use in Turkey.

     

A cluster analysis of chronic obstructive pulmonary disease in dusty areas cohort identified three subgroups

Background

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable clinical manifestations, structural changes, and treatment responses. In a cohort study, we performed a baseline cluster analysis to identify the subgroups of COPD and to assess the clinical outcomes of each subgroup during a 1-year follow-up.

Methods

We analyzed dusty areas cohort comprising 272 patients with COPD. The main factors with the highest loading in 15 variables were selected using principal component analysis (PCA) at baseline. The COPD patients were classified by hierarchical cluster analysis using clinical, physiological, and imaging data based on PCA-transformed data. The clinical parameters and outcomes during the 1-year follow-up were evaluated among the subgroups.

Results

PCA revealed that six independent components accounted for 77.3% of variance. Three distinct subgroups were identified through the cluster analysis. Subgroup 1 included younger subjects with fewer symptoms and mild airflow obstruction, and they had fewer exacerbations during the 1-year follow-up. Subgroup 2 comprised subjects with additional symptoms and moderate airflow obstruction, and they most frequently experienced exacerbations requiring hospitalization during the 1-year follow-up. Subgroup 3 included subjects with additional symptoms and mild airflow obstruction; this group had more female patients and a modest frequency of exacerbations requiring hospitalization.

Conclusions

Cluster analysis using the baseline data of a COPD cohort identified three distinct subgroups with different clinical parameters and outcomes. These findings suggest that the identified subgroups represent clinically meaningful subtypes of COPD.

     

Pseudo current density maps of electrophysiological heart,nerve or brain function and their physical basis

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.

     

Factors associated with pain level in non-cardiac chest pain patients with comorbid panic disorder

Background

Panic disorder (PD) is highly prevalent in patients with non-cardiac chest pain (NCCP). This study aims to explore the role of psychological factors (PD intensity, anxiety sensitivity, heart-related fear, attention and avoidance) common to NCCP and PD in predicting chest pain levels in patients with both conditions.

Methods

This association was investigated in emergency department patients with NCCP and PD receiving either evidence-based treatment of PD or treatment as usual. Patients were assessed at baseline and 14 weeks later for post-treatment.

Results

Only heart-focused fear and attention for cardiac sensations independently explained a significant portion of the variance in baseline pain (n?=?66). At 3 months follow-up (n?=?53), changes in heart-related fear was the only factor independently associated with changes in chest pain intensity. Even in patients with PD, fear specific to cardiac sensations seems to play a central role in determining NCCP intensity.

Conclusion

These results suggest that the efficacy of intervention for patients with PD and comorbid NCCP could be improved by targeting heart-related fear and attention.

Trial registration

NCT00736346

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

Pharmacometabolomics applied to zonisamide pharmacokinetic parameter prediction

Introduction

Zonisamide is a new-generation anticonvulsant antiepileptic drug metabolized primarily in the liver, with subsequent elimination via the renal route.

Objectives

Our objective was to evaluate the utility of pharmacometabolomics in the detection of zonisamide metabolites that could be related to its disposition and therefore, to its efficacy and toxicity.

Methods

This study was nested to a bioequivalence clinical trial with 28 healthy volunteers. Each participant received a single dose of zonisamide on two separate occasions (period 1 and period 2), with a washout period between them. Blood samples of zonisamide were obtained from all patients at baseline for each period, before volunteers were administered any medication, for metabolomics analysis.

Results

After a Lasso regression was applied, age, height, branched-chain amino acids, steroids, triacylglycerols, diacyl glycerophosphoethanolamine, glycerophospholipids susceptible to methylation, phosphatidylcholines with 20:4 FA (arachidonic acid) and cholesterol ester and lysophosphatidylcholine were obtained in both periods.

Conclusion

To our knowledge, this is the only research study to date that has attempted to link basal metabolomic status with pharmacokinetic parameters of zonisamide.

     

<Emphasis Type="Italic">massPix</Emphasis>: an R package for annotation and interpretation of mass spectrometry imaging data for lipidomics

Introduction

Mass spectrometry imaging (MSI) experiments result in complex multi-dimensional datasets, which require specialist data analysis tools.

Objectives

We have developed massPix—an R package for analysing and interpreting data from MSI of lipids in tissue.

Methods

massPix produces single ion images, performs multivariate statistics and provides putative lipid annotations based on accurate mass matching against generated lipid libraries.

Results

Classification of tissue regions with high spectral similarly can be carried out by principal components analysis (PCA) or k-means clustering.

Conclusion

massPix is an open-source tool for the analysis and statistical interpretation of MSI data, and is particularly useful for lipidomics applications.

     

Stress-induced cortisol is associated with generation of non-negative interpretations during cognitive reappraisal

Background

Enhanced processing of emotional stimuli after stress exposure is reported to be associated with stress-induced cortisol. Because enhanced emotional information processing could make cognitive emotion regulation more difficult, it was hypothesized that stress-induced cortisol would be associated with non-negative interpretation generation associated with the cognitive reappraisal processes.

Methods

A total of 36 participants (Mean age?=?21.3 years, SD?=?1.8) watched video clips of depression-related stressful situations before and after the administration of a stress induction task. They were then asked to generate as many non-negative interpretations as possible to reduce the depressive mood. Saliva samples were obtained before and after the stress induction task to measure change in the cortisol level.

Results

Participants were allocated post-hoc to either a responder (n?=?19) or non-responder group (n?=?17) based on the cortisol response to the stress induction task. The number of non-negative interpretations generated following the stress induction task was reduced only in the cortisol responders. The number of post-stress non-negative interpretations was fewer in the responder group when compared by sex, baseline cortisol level, and the number of pre-stress non-negative interpretations, statistically controlled.

Conclusions

Although baseline cortisol and sex may have impacted the results, the results suggest that stress-induced cortisol is associated with difficulty in non-negative interpretation generation during the cognitive reappraisal process.

     

Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome

Context

Patients with chronic fatigue syndrome and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance.

Objective

To determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls.

Design

Assess blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analog scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs.

Setting

Referral practice and research center.

Participants

60 women and 15 men with CFS and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test.

Main outcome measures

Orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof.

Results

CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p < .002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests.

Conclusion

A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition.

     

Effects of specific allergen immunotherapy on biological markers and clinical parameters in asthmatic children: a controlled-real life study

Background

Allergen-specific immunotherapy (AIT) is the only treatment able to change the natural course of allergic diseases. We aimed at investigating the clinical efficacy of SLITOR (Serbian registered vaccine for sublingual allergen specific immunotherapy).

Methods

7–18 years old children with allergic asthma and rhinitis were enrolled and addressed to the active (AIT plus pharmacological treatment) or control (standard pharmacological treatment only) group. Clinical and medications scores, lung function and exhaled FeNO were measured at baseline and at every follow-up.

Results

There was a significant improvement in both nasal and asthma symptom scores as well as in medication score in SLIT group. SLIT showed an important influence on lung function and airway inflammation.

Conclusions

Our data showed that SLITOR was effective not only in terms of patient reported outcomes but an improvement of pulmonary function and decrease of lower airway inflammation were also observed.

     

Unbiased lipidomic profiling reveals metabolomic changes during the onset and antipsychotics treatment of schizophrenia disease

Introduction

Schizophrenia (SCH) is one of the most common psychiatric disorders, which involves impairments in motivation and cognition. The pathological mechanisms underlying SCH are still unknown, and no effective therapies can prevent or treat perfectly the cognitive impairments and deficit symptoms caused by SCH.

Objectives

We aimed to find the lipid expression change in plasma that underlie SCH onset and antipsychotics treatment.

Methods

We performed a data independent acquisition-based untargeted lipidomic approach on a quadrupole-time of flight liquid chromatography coupled to mass spectrometry platform. The plasma lipidomic profiles of SCH patients (n?=?20) pre- and post-antipsychotics treatment were acquired as well as healthy controls (n?=?29). Grouped or paired t-test were used to analyze the data.

Results

Over 1000 features were detected by our lipidomic analysis, of which 445 lipids belonging to 17 lipid species were reliably identified by tandem mass spectrometry. After statistical analysis, 47 lipids belonging to 9 lipid species were found to be dysregulated between naive SCH patients and healthy controls, and 50 lipids belonging to 9 lipid species were found to be dysregulated after antipsychotics treatment. These findings include several new SCH-relevant lipid species such as sphingomyelin, acylcarnitine and ceramide. Four types of lipid expression regulative patterns can be concluded from the above mentioned findings, revealing information about mechanism, side-effect and potential target of antipsychotics.

Conclusions

The work presented here have revealed several new lipid species which are significantly dysregulated in SCH disease development or antipsychotics treatment. These lipids provide new evidence for the pathological studies of SCH and new antipsychotics development, or can be considered as potentially candidate biomarkers for further validation.

     

Characterization of ankylosing spondylitis and rheumatoid arthritis using <Superscript>1</Superscript>H NMR-based metabolomics of human fecal extracts

Introduction

The differences in fecal metabolome between ankylosing spondylitis (AS)/rheumatoid arthritis (RA) patients and healthy individuals could be the reason for an autoimmune disorder.

Objectives

The study explored the fecal metabolome difference between AS/RA patients and healthy controls to clarify human immune disturbance.

Methods

Fecal samples from 109 individuals (healthy controls 34, AS 40, and RA 35) were analyzed by ¹H NMR spectroscopy. Data were analyzed with principal component analysis (PCA) and orthogonal projection to latent structure discriminant (OPLS-DA) analysis.

Results

Significant differences in the fecal metabolic profiles could distinguish AS/RA patients from healthy controls but could not distinguish between AS and RA patients. The significantly decreased metabolites in AS/RA patients were butyrate, propionate, methionine, and hypoxanthine. Significantly increased metabolites in AS/RA patients were taurine, methanol, fumarate, and tryptophan.

Conclusion

The metabolome variations in feces indicated AS and RA were two homologous diseases that could not be distinguished by ¹H NMR metabolomics.